Noradrenergic receptor blockade of the NTS attenuates the mnemonic effects of epinephrine in an appetitive light-dark discrimination learning task

These experiments examined the contribution of noradrenergic neurons in the nucleus of the solitary tract (NTS) in mediating the memory-facilitating effects of epinephrine. In Experiment 1, saline or 0.05 or 0.1 mg/kg of epinephrine was given intraperitoneally (ip) to rats after the second day of training in a light-dark Y-maze discrimination task. On a 20-trial retention test given 2 and 7 days later, the 0.1 mg/kg epinephrine group made significantly more correct responses than controls and required fewer trials to reach criterion. In Experiment 2, phosphate-buffered saline or the noradrenergic antagonist dl-propranolol (0.3 or 1.0 microg/0.5 microl) was infused into the NTS prior to an ip injection of saline or 0.1 mg/kg of epinephrine. The memory-enhancing effects of epinephrine were attenuated by the infusion of 0.3 microg/0.5 microl of dl-propranolol into the NTS. These findings indicate an involvement of NTS noradrenergic neurons in mediating the effects of peripheral epinephrine on memory storage processes.     

Epinephrine Effects on Memory Are Not Dependent on Hepatic Glucose Release

Epinephrine released or administered soon after a given training task modulates memory processes. Since epinephrine does not readily cross the blood–brain barrier, studies have suggested that some of the central effects of epinephrine might be mediated by peripheral release of glucose. These experiments examined the involvement of blood glucose levels in the posttraining effects of peripherally administered epinephrine. The effects of the administration of epinephrine (25 and 625 mg/kg) on memory of an inhibitory avoidance task were evaluated in fed and fasted rats (depleted glycogen stores in liver). Blood glucose levels after the task in each group were also measured. Female Wistar rats were divided in two groups. Fed and 48-h-fasted animals were submitted to the inhibitory avoidance task and received ip epinephrine or saline immediately after training. The test session was carried out 48 h after training. Epinephrine (25 or 625 mg/kg) caused an increased glycemia in fed rats, but no effect was observed in fasted animals. Administration of epinephrine 25 mg/kg induced a facilitation of memory, while epinephrine 625 mg/kg impaired retention (either in fasted or in fed animals). There was no relation between increased glycemia induced by epinephrine and its effects on memory, since this drug presented its classical effects independently of the previous state of the animal (fed or fasted). The results of the present study suggest that the effects of systemic released or administered epinephrine on memory processes are not dependent on hepatic glucose release.     

Effect of sulpiride on amphetamine-induced activity and stereotyped locomotion

To investigate the hypothesis that sulpiride potentiates stereotyped locomotion at an intermediate dose of amphetamine, rats were assigned to one of four treatment groups (n=7 per group): vehicle + saline; 20 mg/kg sulpiride + saline; vehicle + 3.5mg/kg amphetamine; 20 mg/kg sulpiride + 3.5 mg/kg amphetamine. An automated tracking system was used to record distance moved and sequences of movements between quadrants in a circular open-field. The results showed that amphetamine increased horizontal distance moved, and increased the number and proportion of thigmotaxic trips around the perimeter of the apparatus. Sulpiride reduced amphetamine-induced hyperactivity and the number of perimeter trips, but had no effect on the proportion and maximum run length of perimeter trips. Thus sulpiride reduces the hyperactivity produced by an intermediate dose of amphetamine, but does not appear to affect the stereotyped nature of locomotion under the drug.     

Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.     

Epinephrine administration increases neural impulses propagated along the vagus nerve: Role of peripheral beta-adrenergic receptors

A significant number of animal and human studies demonstrate that memories for new experiences are encoded more effectively under environmental or laboratory conditions which elevate peripheral concentrations of the hormone epinephrine and in turn, induce emotional arousal. Although this phenomenon has been replicated across several learning paradigms, understanding of how this arousal related hormone affects memory processing remains obscure because epinephrine does not freely enter into the central circulation to produce any direct effects on the brain. This study examined whether epinephrine's actions on the CNS may be mediated by the initial activation of peripheral vagal fibers that project to the brain. The vagus was selected as a candidate for this role since it is densely embedded with beta-adrenergic receptors and the peripheral endings of this nerve innervate a broad spectrum of sensory organs that are directly affected by epinephrine release. Electrophysiological recordings of cervical vagal activity was measured over 110 min in urethane-anesthetized Sprague-Dawley rats given saline, epinephrine (0.3 mg/kg), the peripherally acting beta-adrenergic antagonist sotalol (2.0 mg/kg), or a combination of sotalol followed 15 min later by an injection of epinephrine. Epinephrine produced a significant increase in vagal nerve firing 10 min post-injection (p < .05) relative to controls and neural impulses recorded from the vagus remained significantly elevated for the remaining 55 min collection period. The excitatory actions of epinephrine were not observed in groups given an identical dose of the hormone after peripheral beta-adrenergic receptor blockade with sotalol. These findings demonstrate that neural discharge in vagal afferent fibers is increased by elevations in peripheral concentrations of epinephrine and the significance of these findings in understanding how epinephrine modulates brain limbic structures to encode and store new information into memory is discussed.     

Diazepam prevents post-training drug effects related to state dependency, but not post-training memory facilitation by epinephrine

Rats were trained and tested in a step-down inhibitory avoidance task (0.3-mA footshock). Training-test interval was 6 h. In Experiment 1, animals received, 1 h before training, an ip injection of vehicle or diazepam (2.0 mg/kg) and, 30 s after training and/or 30 min prior to testing, ip saline, epinephrine (6.25 micrograms/kg or 125.0 micrograms/kg), naloxone (0.5 mg/kg), or beta-endorphin (1 micrograms/kg). In the vehicle-pretreated animals, post-training epinephrine (6.25 micrograms/kg) and naloxone enhanced, and post-training beta-endorphin and epinephrine (125.0 micrograms/kg) reduced, retention test performance; and pretest beta-endorphin and epinephrine (125.0 micrograms/kg) reversed the latter effect and enhanced retention on their own. Diazepam lowered memory scores on its own and prevented all other drug effects with the exception of post-training facilitation by epinephrine (6.25 micrograms/kg). In previous papers it was shown that post-training facilitation by epinephrine is due to an influence on storage processes, whereas all the other drug effects described above result from the post-training establishment of state dependency to either beta-endorphin or epinephrine, and therefore to a process involving further acquisition and storage. The present findings suggest that diazepam selectively hindered the acquisition and/or storage processes involved in state dependency. This conclusion is strengthened by the findings from Experiment 2, which showed, using a classic 2 x 2 design, that diazepam itself did not induce state dependency but, rather, depressed acquisition and/or storage of the avoidance task.     

Scheduled running wheel activity indexes the specificity of pharmacological anorexia.

Nondeprived male Sprague-Dawley rats that were given scheduled access to running wheels for 60 min daily ran immediately and energetically. Intraperitoneal injections of 400 micrograms/kg pancreatic glucagon and 0.15 microgram/kg cholecystokinin octapeptide had no effect on scheduled running, but significantly inhibited feeding when the rats were offered condensed milk instead of access to the running wheels. This is consistent with the hypothesized function of these peptides as postprandial satiety signals. In contrast, 0.5 mg/kg amphetamine and 75 microM/kg LiCl, which produced similar degrees of anorexia, inhibited running by about 50%. Amphetamine, but neither peptide, also inhibited water drinking and disrupted the behavioral sequence of postprandial satiety. The distance run during scheduled running tests was inversely related to body weight, but the patterns of the drugs' effects were not altered by baseline running differences. Scheduled wheel running is a robust consummatory behavior that appears to provide a relatively valid, simple, and sensitive test of the behavioral specificity of pharmacological anorexia.     

Variable-interval schedules of timeout from avoidance: effects of chlordiazepoxide, CGS 8216, morphine, and naltrexone.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other occasionally (variable-interval schedule) produced a 2-min timeout during which the shock-postponement schedule was suspended and its correlated stimuli were removed. These procedures provided a baseline for studying the effects of drugs on behavior maintained by different sources of negative reinforcement (shock avoidance and timeout from avoidance). Experiment 1 studied a benzodiazepine agonist, chlordiazepoxide, and antagonist, CGS 8216. Chlordiazepoxide (2.5-30 mg/kg) had little effect on avoidance responding except at higher doses, when it reduced responding. By comparison, responding on the timeout lever was increased in 5 of 6 rats. These effects were reversed by CGS 8216 (2.5-5 mg/kg) in the 2 rats tested, but CGS 8216 had no effect by itself. Experiment 2 studied an opiate agonist, morphine, and antagonist, naltrexone, with 3 rats. Morphine's (2.5-20 mg/kg) effects were opposite those of chlordiazepoxide: At doses that either increased or had no effect on avoidance responding, morphine depressed timeout responding. Naltrexone (5 mg/kg) reversed these actions but had no effect by itself.     

Amphetamine and morphine produce a conditioned taste and place preference in the house musk shrew (Suncus murinus)

Rats have been shown to avoid consuming a flavor, but prefer a location, previously paired with amphetamine or morphine. A series of 4 experiments evaluated the hedonic properties of amphetamine and morphine in the house musk shrew (Suncus murinus), an insectivore that (unlike rats) is capable of vomiting when exposed to toxins. Unlike rats, amphetamine (20 mg/kg) and morphine (20 mg/kg) produced both a conditioned sucrose (0.3 M) and saccharin (0.1%) preference in shrews (administered intraperitoneally), when measured by both a 1- and a 2-bottle test. At the same dose, both drugs also produced a place preference in shrews. These results suggest that the potential of rewarding drugs to produce taste avoidance may vary on the basis of the ability of the species to vomit.     

Glucose modulation of memory storage processing

Epinephrine, derived from the adrenal medulla, enhances memory storage for several forms of learning. One physiological action of this hormone is to liberate hepatic glucose stores. This experiment tested the possibility that glucose could itself enhance memory. Rats were water deprived, pretrained to drink, pretrained to drink in the behavioral apparatus, and then trained in a one-trial inhibitory (passive) avoidance task. Immediately after the training footshock, the animals each received an injection of glucose (1.0-500 mg/kg). When tested for retention 24 h later, the animals which received 10 or 100 mg/kg doses of glucose exhibited enhanced retention performance; higher and lower doses had no significant effect on the memory tests. Also, glucose injections (100 mg/kg) delayed by 1 h after training had no effect on the retention tests. These findings suggest that the increase in plasma glucose levels subsequent to epinephrine injection may contribute to the effects of epinephrine on memory. In addition, the results suggest that peripheral glucose levels may exert important influences on memory storage.     

Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory

Two studies were conducted to test the ability of post-trial amphetamine treatment to improve later recall in a nonaversively motivated task. These studies utilized 8- and 12-arm radial mazes, respectively, with an 11-h retention interval imposed after the rat traversed half the arms of the maze (termed, the to-be-remembered-event, or TBRE). In Experiment 1, the rats were injected with amphetamine (0, .25, and .50 mg/kg) immediately after the TBRE. Because the drug treatment improved retention, a time dependency study was conducted in which the drug (0 and .33 mg/kg) was administered 0, 3, and 6 h after the TBRE. The finding that amphetamine injection at 0, but not 3, h post-trial improved later recall indicates that the benefit derived from the former treatment is not due to proactive influences at the time of the retention test. Drug treatment 6 h post-trial produced a borderline improvement of recall; possible mechanisms are discussed. Two conclusions can be drawn from these results: (1) amphetamine administration can improve recall under conditions in which this effect cannot be attributed to alterations in information processing during either the learning or the retention sessions, indicating that the drug modulates memory storage processes; and (2) amphetamine treatment can improve working memory, thus excluding an alternative interpretation for the previous reports of impaired short-term memory in animals, all of which entailed assessments of working memory. The possibility remains, however, that the impairment seen in these tasks reflects the requirement for erasure of information from previous trials within each daily session, rather than the duration of the retention interval.     

Glucose and physostigmine effects on morphine- and amphetamine-induced increases in locomotor activity in mice

Recent findings indicate that glucose antagonizes several behavioral effects of cholinergic antagonists and augments those of cholinergic agonists. For example, scopolamine elicits increased locomotor activity, an action which is attenuated by glucose and by combined treatment with glucose and physostigmine at doses which are individually without effect. Opiate and catecholamine agonists, such as morphine and amphetamine, also elicit hyperactivity. The present study examined interactions of glucose and physostigmine with morphine- and amphetamine-induced hyperactivity. Mice received saline, morphine (10 mg/kg), or amphetamine (1 mg/kg) 50 min prior to testing, followed by saline, physostigmine (0.01, 0.05, 0.1, or 0.2 mg/kg), or glucose (10, 50, 100, or 500 mg/kg) administered 20 min prior to activity testing in an open field. Physostigmine significantly attenuated both morphine- and amphetamine-induced increases in activity, but higher doses were required to attenuate the effects of amphetamine. Like physostigmine, glucose significantly attenuated morphine-induced activity levels, but unlike physostigmine, glucose did not attenuate amphetamine-induced activity. Thus, the behavioral effects of morphine were more susceptible to modification by physostigmine and glucose than were the effects of amphetamine. The attenuation of morphine-induced hyperactivity demonstrates a similarity between glucose and cholinergic agonists, and also indicates that glucose may inhibit, directly or indirectly, opiate functions. More generally, these findings add to the evidence that circulating glucose levels selectively influence a growing list of behavioral and neurobiological functions.     

Effects of fluoxetine on play dominance in juvenile rats

In a series of three studies, we investigated the influence of a selective serotonin re-uptake inhibitor (fluoxetine) on the rough-and-tumble play of juvenile rats. In Experiment 1, both members of eight pairs of solitary-housed juvenile rats received either vehicle, 2.5, 5, or 10 mg/kg fluoxetine in a counterbalanced within-subject design 20 min before being allowed to play for 5 min periods on four successive test days. The 5 and 10 mg/kg pretreatments significantly reduced incidence of pins during play without affecting dorsal contacts. In Experiment 2, one member of each of 19 established play pairs received 5 mg/kg fluoxetine 20 min before play, while the other member received vehicle. Dominant rats showed no reduction in pins as a result of fluoxetine treatment, but subordinate rats who received fluoxetine exhibited significant reductions in pins. Subsequent dyadic analyses indicated that in pairs where the subordinate animal received fluoxetine, dominant animals maintained their pinning advantage over the 10 days of testing, but in pairs where the dominant animals received fluoxetine, this pinning asymmetry diminished. In Experiment 3, we replicated the above procedure with inexperienced play pairs, to control for the effects of prior social learning. Fluoxetine treatment (5 mg/kg) significantly reduced both pins and dorsal contacts in all treated rats. The results indicate that fluoxetine can reduce the playful pins of juvenile rats, but that prior social learning mediates the strength of these effects. © 1996 Wiley-Liss, Inc.     

The behavioral effects of depletions of brain serotonin induced by 5,7-dihydroxytryptamine vary with time after administration

Ether-anesthetized Sprague-Dawley rats were depleted of brain serotonin (5HT) by intraventricular injections of 50 micrograms 5,7-dihydroxtryptamine (57DHT). Oral pretreatment with 25 mg/kg desmethylimipramine was used to protect brain noradrenergic neurons from 57DHT. Liquid chromatographic assays revealed that this treatment did not significantly alter catecholamine levels but depleted hippocampal 5HT by 92% and striatal 5HT by 45%. Three or eleven days after lesioning, locomotor and exploratory behavior was characterized in separate groups of animals with a behavioral pattern monitor (BPM). On Days 4 and 12, the animals were retested following saline or 1.0 mg/kg amphetamine. Three days after depletion, lesioned rats exhibited a decrease rate of habituation of locomotor activity relative to controls. When challenged with amphetamine (1.0 mg/kg), 5HT-depleted rats exhibited increased corner and decreased center activity, as well as stereotyped patterns of locomotion. Eleven days following lesion, 5HT-depleted rats exhibited habituation rates greater than controls; amphetamine challenge yielded patterns of activity similar to those of control animals. These results show that central serotonergic pathways play an important role in modulating both spontaneous and amphetamine-elicited activity in rats, and that compensatory mechanisms operate over time to alter the behavioral effects of 57DHT-induced depletions of brain 5HT.     

Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Steroid modulation of cognitive function has focused on estrogen (E(2)), but progestins naturally co-vary with E(2) and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E(2) and progestins vary, and when E(2) and/or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17beta-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E(2) and P, immediately after training in the object placement task, performed significantly better when tested 4h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E(2) or P with a 1.5h delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: ovx rats administered post-training E(2), which has a high affinity for both E(2) receptor (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERalpha than ERbeta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E(2) and/or P are naturally elevated or when E(2), the ERalpha selective ER modulator PPT, P, or its metabolite, 3alpha,5alpha-THP, are administered post-training.     

Effects of opiate antagonists on spatial memory in young and aged rats

The effects of post-training opiate antagonist administration on spatial memory were assessed in young and aged male Long Evans rats. In Experiment I rats were trained to visit each arm of an eight-arm radial maze once in a session to obtain a food reward placed at the end of each arm. During training aged rats required significantly more trials to achieve criterion performance when compared to young mature rats. However, administration of the opiate antagonist naloxone (2.0 mg/kg) immediately after each training trial did not significantly alter the rate of achieving accurate performance in either age group. In Experiment II young and aged rats that were previously trained to a comparable criterion on the radial maze were tested on the same maze apparatus in novel spatial environments. When animals were exposed to novel spatial information, the effects of post-trial opiate antagonists were examined using a within-subjects counter-balanced design. In Experiment IIa naloxone (2 mg/kg) enhanced the performance of both young and aged rats. In Experiment IIB naltrexone (1.0 mg/kg) was found to have a comparable effect of enhancing the performance of both age groups. In addition, in Experiment IIb a significant age-related deficit was found in rats tested in novel spatial environments. These results indicate that opiate antagonists are capable of improving memory for new spatial information in both young and aged rats on a task that is sensitive to behavioral deficits during normal aging.     

Shuttle-box avoidance learning in mice: improvement by glucose combined with stimulant drugs

Glucose was tested alone or in combination with two stimulant drugs, amphetamine and nicotine, in mice of the CD-1 strain subjected to five daily shuttle-box training sessions. Pretraining intraperitoneal administration of glucose (50 or 100 mg/kg) had no effect, while amphetamine and nicotine, given alone, significantly improved avoidance acquisition at a dose of 0.5 mg/kg, but not 0.025 mg/kg. Significant improvement of avoidance learning was also produced by a combination of glucose with the lower dose of amphetamine or nicotine. This enhancing action, produced by a combination of glucose and stimulant drugs, at doses ineffective by themselves, might be due to a concomitant cholinergic and dopaminergic activation, induced by glucose and stimulant drugs, respectively.     

The effects of training, epinephrine, and glucose injections on plasma glucose levels in rats

Recent findings indicate that a post-training injection of glucose enhances memory storage, suggesting that release of glucose into plasma may mediate the effects of epinephrine and perhaps other treatments on memory. The present experiment examined the effects of handling, inhibitory (passive) avoidance training, epinephrine and glucose injections on plasma glucose levels in Sprague-Dawley rats. Handling produced a small, but significant, transient increase in plasma glucose above basal levels. Saline injections caused a similar increase in circulating glucose levels. Inhibitory avoidance training with high footshock (2.0 mA, 2.0 s) resulted in significant increases in plasma glucose levels above those of low (0.5 mA, 0.75 s) and unshocked animals suggesting that glucose release is responsive to inhibitory avoidance training. Subcutaneous injections of epinephrine (0.01-1.0 mg/kg), or glucose (10-1000 mg/kg) significantly elevated glucose levels above those of saline-injected animals in a dose-dependent manner. Memory facilitating doses of epinephrine and glucose resulted in increases in plasma glucose levels similar to those seen in rats trained with high footshock. Higher doses of epinephrine and glucose resulted in further increases in circulating glucose, to levels significantly greater than those of memory facilitating doses. These results suggest that memory modulation, both endogenous and in response to epinephrine injections, may be mediated in part by circulating glucose levels. Thus, the findings of these experiments support the view that circulating glucose levels regulate the efficacy of neural memory storage processes.     

Simple disturbance of the dam in the neonatal period can alter haloperidol-induced catalepsy in the adult offspring

Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood.     

Effects of gonadectomy and androgen supplementation on attention in male rats

Androgens are hypothesized to enhance aspects of mnemonic processing. However, it is unclear whether the memory improvement is associated with changes in earlier aspects of information processing, such as attention. The present experiments examined the effects of gonadectomy or supplementation with testosterone or dihydrotestosterone on performance of male rats in a two-lever attention task that required discrimination of visual signals and non-signals. In Experiment 1, Long-Evans rats were trained in the attention task and then underwent gonadectomy or sham-surgery. Postsurgically, animals were tested for 20 sessions in the attention task and then received manipulations designed to increase attentional demands. Gonadectomized and sham-treated animals performed similarly during immediate postsurgical testing and across all manipulations. Finally, the effects of administering the muscarinic receptor antagonist scopolamine (0, 0.1, and 0.2 mg/kg) on attentional performance were assessed for all animals. Scopolamine decreased accuracy of signal detection but did not differentially affect gonadectomized and sham-treated animals. In Experiment 2, a new group of rats (not gonadectomized) was trained to perform the attention task and subsequently administered testosterone (0, 0.1, and 0.5 mg/kg) or dihydrotestosterone (0, 0.1, and 0.5mg/kg) prior to performing the standard version of the attention task and in the presence of a visual distractor. Testosterone (0.5 mg/kg) decreased accuracy on non-signal trials and, at 0.1 mg/kg, decreased latencies to retrieve a reward. Dihydrotestosterone (0.5 mg/kg) decreased accuracy on non-signal trials during visual distractor sessions. The present data do not support the hypothesis that alterations in attention critically mediate androgen-induced changes in mnemonic processing. Supra-physiological androgen levels appear to be capable of impairing attentional processing.