Aggressive behavior inhibition by serotonin and quipazine injected into the amygdala in the rat

The effects on aggressive behavior, open-field activity, and pain threshold of bilateral microinjections of serotonin (20 micrograms) and quipazine (20 micrograms), the direct serotonergic receptor agonist, into the cortico-medial amygdala were investigated in Wistar rats. Both drugs significantly prolonged the attack latency in isolated killer rats (predatory aggression model), and suppressed the incidence of aggressive postures/attacks in shock-induced fighting test (affective aggression). The only difference in the open-field behavior was the lower number of central square entries in drug-treated compared to saline-injected rats. None of the substances produced any significant change in jump threshold. It is concluded that stimulation of serotonin receptors within the amygdala produces inhibition of affective and muricidal behavior in isolated rats. The effect does not seem to be dependent on changes in general activity and pain sensitivity.     

Modification of the rat's acoustic startle response by antecedent visual stimulation.

Male hooded and albino rats were exposed to a light flash followed at various temporal intervals by a startle-eliciting 117 db. (re 20 muN/m2) burst of white noise. The visual stimulus engendered startle response inhibition (maximally when the lead time was 64-250 msec) as well as startle response latency reduction (maximally when the lead time was 2-8 msec). The temporal functions for the effects of visual stimuli paralleled those previously reported for startle modification by acoustic events. Further study revealed that, given optimal lead times, inhibition is produced reliably by weaker visual stimuli (3 X 10-6 cd-sec/cm2) than latency reduction (3 X 10-4 cd-sec/cm2). This differential sensitivity to visual stimuli is also analogous to previously reported findings for events in the acoustic environment. It reveals that the neural mechanisms that mediate latency reduction and inhibition can be engaged by either acoustic or visual stimulation.     

EFFECTS OF LYSERGIC ACID DIETHYLAMIDE (LSD-25) ON NORMAL SUBJECTS IN A SCHIZOPHRENIA-DISCRIMINATING TEST BATTERY

Psychological tests with differing sensitivity to schizophrenic reactions were administered to eight normal subjects after oral intake of 75–100 μ g LSD-25. Control data were obtained from placebo trials. Six of the tests were chosen as sensitive to schizophrenic reactions, two tests as so-called 'hold' tests, and another test as a measure of attention, which is supposed to be reduced by LSD. Significantly lower results were obtained on four of the six sensitive tests after LSD, on one of the 'hold' tests, and on the attention test.     

The effect of rearing environments on the contrafreeloading phenomenon in rats

Eight naive rats were reared in enriched or impoverished environments for 39 days after weaning and then lived in operant chambers, in which they could obtain food pellets freely or by lever pressing, for 25 or 30 days. The animals raised in an impoverished environment acquired the bar-press response quickly when placed in the operant chambers and maintained a preference for obtaining food via bar pressing. Animals raised in an enriched environment did not learn to lever press, as demonstrated by low levels of responding and the lack of bar pressing when free food was subsequently removed. It was concluded that restricting animals' postweaning environments facilitated learning in a choice situation, probably because of increased activity levels. The results are interpreted in relation to previous studies on rearing environments and on contrafreeloading.     

Memory for Duration: Role of Hippocampus and Medial Prefrontal Cortex

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).     

Peripheral 8-OH-DPAT and scopolamine infused into the frontal cortex produce passive avoidance retention impairments in rats

The present study determined whether peripheral injections of the 5HT(1A) agonist (8-OH-DPAT), scopolamine infusions into the frontal cortex, or a combination of both drug treatments would produce impairments in rats trained on passive avoidance. Using a 2x2 design, rats were infused with either bacteriostatic water or 30 microg/1 microl of scopolamine HCl into the frontal cortex 30 min before being trained on passive avoidance. This was followed by injections (ip) of either 0.1% ascorbic acid/bacteriostatic water or 30 microg/kg of 8-OH-DPAT 15 min later. All subjects were tested for retention 72h later. At test, the initial latency to enter into the black shocked compartment and the total time spent in the white safe compartment (TTW) were recorded. Analysis of the latency data indicated that scopolamine and 8-OH-DPAT, when administered singly or in combination, produced amnesia for the task. Assessment of TTW scores, however, revealed that of the three drug-treated groups, only animals treated with 8-OH-DPAT alone tended to avoid the previously shocked black compartment and spend more time in the white safe compartment. These data indicate that either stimulating 5-HT(1A) or blocking frontal cortical muscarinic receptors at training impairs passive avoidance performance and that the deficit following the latter treatment is somewhat more extensive. Implications for the role frontal cortical muscarinic and 5HT(1A) receptors play in learning and memory are discussed.     

The interactive effects of alcohol and temazepam on P300 and reaction time

The present research investigated the separate and interactive effects of the minor tranquilizer, temazepam, and a low dose of alcohol on the amplitude and latency of P300 and on reaction time. Twenty-four participants completed four drug treatments in a repeated measures design. The four drug treatments, organised as a fully repeated 2 x 2 design, included a placebo condition, an alcohol only condition, a temazepam only condition, and an alcohol and temazepam combined condition. Event-related potentials were recorded from midline sites Fz, Cz, and Pz within an oddball paradigm. The results indicated that temazepam, with or without the presence of alcohol, reduced P300 amplitude. Alcohol, on the other hand, with or without the presence of temazepam, affected processing speed and stimulus evaluation as indexed by reaction time and P300 latency. At the low dose levels used in this experiment alcohol and temazepam appear not to interact, which suggests that they affect different aspects of processing in the central nervous system.     

Procurement time as a determinant of meal frequency and meal duration.

Foraging involves the expenditure of both time and effort in the acquisition of food; animals typically modify their meal patterns so as to reduce these expenditures or costs. The contribution of time, as compared with effort, to the overall cost perceived by an animal is not known. We investigated the effect of foraging time as a cost independent of effort by measuring the meal patterns of rats living in a laboratory foraging simulation in which they earned all their daily intake. They pressed a bar once to initiate an interval (procurement interval) leading to the presentation of a large cup of food from which they could eat a meal of any size. As the length of the interval increased from 1 s to 46 hr, meal frequency decreased regularly. Meal size increased in a compensatory fashion, and total daily intake was conserved through an interval of 23 hr. The changes in meal frequency occurred because of changes in the rat's latency to bar press after each meal. The functions relating meal frequency and size to the procurement interval were of the same shape as those seen when cost is the completion of a bar-press requirement, which entails the expenditure of both effort and time. When the bar-press requirement was increased to 10, meal frequency was reduced, but time and effort did not appear to simply add together in the rat's perception of cost. These data reveal that time is preceived to be a cost by rats foraging in this laboratory environment. These results suggest that the time parameters of foraging are different from those of consumption.     

LSD response in Eysenckian trait types identified by polypredictive CFA

The four personality type combinations derived from high and low extraversion () and high and low neuroticism () have been related to response patterns composed of three symptoms (affective disturbances, thinking disturbances, and blackouts) scored as present (+) or absent (−) after a single oral dose of the hallucinogenic drug LSD-25. Hypotheses for expected response patterns for each personality group were derived from a data set obtained by Kohnen and Lienert (1987). Significance of associations was tested by two strategies of polyprediction configural frequency analysis (CFA): multiple uniprediction and biprediction CFA. Both strategies yielded a significant hyperpresentation of all three symptoms present in E+N+ (hysterics), merely thinking disorders in dysthymics (E−N+), merely affective symptoms in E+N− (stable extraverts), and merely blackouts in N−E− (stable introverts). Authors tried to relate these symptoms to Kretschmer's temperament types and could afterwards show by a chessboard modification of prediction CFA, that by applying two combined hypotheses for two personality types each, the significance of the predicted associations could be increased.     

The effect of ethanol treatment on social behavior in male rats

The effect of 0.50 g/kg of EtOH in male rats interacting with a stimulus male juvenile in a newly developed test of social interaction was examined. The adult male rats were treated with EtOH (8.0 to 12.0 g/kg/day) or equicaloric dextrin maltose for 2 weeks (studies 1 and 2) or 8 weeks (study 3) and social interaction was assessed both before and after chronic drug treatment was ended in study 1 and after chronic drug treatment was ended in studies 2 and 3. It was found that prior to chronic drug treatment, in study 1, 0.50 g/kg of EtOH increased both aggressive behavior and time spent interacting with the stimulus juvenile male from the first presentation of the juvenile to the second presentation (20 min apart) while saline injection decreased it. After chronic drug treatment was ended, in study 1 animals treated chronically with EtOH were more aggressive when they were not intoxicated than when they had been treated with 0.50 g/kg of EtOH. In studies 2 and 3, after chronic drug treatment was ended, aggressive behavior and time spent interacting with the juvenile were greater in the animals treated chronically with EtOH, regardless of whether they were injected with saline or 0.50 g/kg of EtOH. The results of these studies showed that chronic EtOH treatment can produce long-lasting changes in social behavior after drug treatment is over and can alter the animal's normal response to EtOH in a social setting.     

Forgetting of an operant response: Physostigmine-produced increases in escape latency in rats as a function of time of injection

Latency of a fixed ratio (FR) 3 escape response in rats was found to be a U-shaped function of the interval between training and injection of the anticholinesterase drug physostigmine, for intervals from 30 min. to 5 days between training and injection. An increase in FR 3 escape latency was found at 28 days. FR 1 escape groups produced a latency curve of a shape similar to that of the FR 3 group. These data confirm the results of earlier experiments using a different training procedure, and a different response measure. These results are consistent with the theory that the physiological correlate of rat memory lies in synaptic change.     

Chronic, severe hypertension does not impair spatial learning and memory in Sprague-Dawley rats

This study tested the hypothesis that long-term hypertension impairs spatial learning and memory in rats. In 6-wk-old Sprague-Dawley rats, chronic hypertension was induced by placing one of three sizes of stainless steel clips around the descending aorta (above the renal artery), resulting in a 20–80-mm Hg increase of arterial pressure in all arteries above the clip, that is, the upper trunk and head. Ten months later, the rats were tested for 5 d in a repeated-acquisition water maze task, and on the fifth day, they were tested in a probe trial; that is, there was no escape platform present. At the end of the testing period, the nonsurgical and sham control groups had similar final escape latencies (16±4 sec and 23±9 sec, respectively) that were not significantly different from those of the three hypertensive groups. Rats with mild hypertension (140–160 mm Hg) had a final escape latency of 25±6 sec, whereas severely hypertensive rats (170–199 mm Hg) had a final escape latency of 21±7 sec and extremely hypertensive rats (>200 Hg) had a final escape latency of 19±5 sec. All five groups also displayed a similar preference for the correct quadrant in the probe trial. Together, these data suggest that sustained, severe hypertension for over 10 mo is not sufficient to impair spatial learning and memory deficits in otherwise normal rats.     

Behavioral economics of concurrent ethanol-sucrose and sucrose reinforcement in the rat: effects of altering variable-ratio requirements.

These experiments examined the own-price and cross-price elasticities of a drug (ethanol mixed with 10% sucrose) and a nondrug (10% sucrose) reinforcer. Rats were presented with ethanol-sucrose and sucrose, both available on concurrent independent variable-ratio (VR) 8 schedules of reinforcement. In Experiment 1, the variable ratio for the ethanol mix was systematically raised to 10, 12, 14, 16, 20, and 30, while the variable ratio for sucrose remained at 8. Five of the 6 rats increased ethanol-reinforced responding at some of the increments and defended baseline levels of ethanol intake. However, the rats eventually ceased ethanol-reinforced responding at the highest variable ratios. Sucrose-reinforced responding was not systematically affected by the changes in variable ratio for ethanol mix. In Experiment 2, the variable ratio for sucrose was systematically increased while the ethanol-sucrose response requirement remained constant. The rats decreased sucrose-reinforced responding and increased ethanol-sucrose-reinforced responding, resulting in a two- to 10-fold increase in ethanol intake. Experiment 3 examined the substitutability of qualitatively identical reinforcers: 10% sucrose versus 10% sucrose. Increases in variable-ratio requirements at the preferred lever resulted in a switch in lever preference. Experiment 4 examined whether 10% ethanol mix substituted for 5% ethanol mix, with increasing variable-ratio requirements of the 5% ethanol. All rats eventually responded predominantly for the 10% ethanol mix, but total amount of ethanol consumed per session did not systematically change. In Experiment 5, the variable-ratio requirements for both ethanol and sucrose were simultaneously raised to VR 120; 7 of 8 rats increased ethanol-reinforced responding while decreasing sucrose-reinforced responding. These data suggest that, within this ethanol-induction procedure and within certain parameters, demand for ethanol-sucrose was relatively inelastic, and sucrose consumption was independent of ethanol-sucrose consumption. Demand for sucrose, on the other hand, was relatively elastic, and ethanol-sucrose readily substituted for it. The results are discussed in terms of applying a behavioral economic approach to relationships between drug and nondrug reinforcers.     

Leupeptin, a thiol proteinase inhibitor, causes a selective impairment of spatial maze performance in rats

The effects of chronic intraventricular infusion of leupeptin, a potent inhibitor of thiol proteinases, were tested on ingestive behaviors, escape and avoidance conditioning, and spatial memory in rats. The drug did not detectably influence feeding, drinking, body temperature, or the latency to escape from a mild footshock or inhibitory avoidance behavior. However, rats treated with leupeptin made numerous errors ( reentries ) in an eight-arm spatial maze. These results are interpreted as supporting the hypothesis that calcium-activated thiol proteinases are involved in the formation of certain types of memory.     

Psychostimulant-induced behavior as an animal model of obsessive-compulsive disorder: an ethological approach to the form of compulsive rituals

Rats treated chronically with the D2/D3 dopamine receptor agonist quinpirole show a pattern of behavior that meets a set of ethologically derived criteria of compulsive behavior in obsessive-compulsive disorder (OCD). Moreover, in both quinpirole-treated rats and OCD patients, the structure of compulsive rituals appear similar in being composed of relatively few motor acts that are organized in a flexible yet recurrent manner. In addition, the development of compulsive behavior in quinpirole-treated rats is attenuated by the OCD pharmacotherapeutic drug clomipramine. These similarities support the validity of quinpirole-treated rats as a psychostimulant-induced animal model of OCD. Considering that the induction of compulsive behavior in the rat model involves chronic hyperstimulation of dopamine receptors, this raises the possibility that dopaminergic mechanisms may play a role in OCD, at least in some subtypes of this disorder.     

Effects of haloperidol on schedule-induced polydipsia.

In dose-related amounts, the drug haloperidol attenuated schedule-induced drinking by rats prefed with 0.01-mg drug added to 0, 25, 50, 75 or all of 100 Noyes 45-mg pellets. Drug pellets also induced less drinking than did regular Noyes pellets by rats that obtained these pellets at 1-min intervals by bar pressing. Haloperidol also reduced bar pressing and, temporarily, rate of reinforcement. The results appeared not to be due to a general sedative effect of haloperidol but to its selective power to reduce angiotensin-induced drinking. Thus, schedule-induced drinking, which is abnormal in not causing satiation, is controllable by a drug that interferes with the renin-angiotensin hormone system thought to regulate normal drinking.     

Effects of chronic cocaine administration on spatial learning and hippocampal spine density in two genetically different strains of rats

Lewis and Fischer-344 rats have been proposed as an addiction model because of their differences in addiction behaviour. It has been suggested that drug addiction is related to learning and memory processes and depends on individual genetic background. We have evaluated learning performance using the eight-arm radial maze (RAM) in Lewis and Fischer-344 adult rats undergoing a chronic treatment with cocaine. In order to study whether morphological alterations were involved in the possible changes in learning after chronic cocaine treatment, we counted the spine density in hippocampal CA1 neurons from animals after the RAM protocol. Our results showed that Fischer-344 rats significantly took more time to carry out test acquisition and made a greater number of errors than Lewis animals. Nevertheless, cocaine treatment did not induce changes in learning and memory processes in both strains of rats. These facts indicate that there are genetic differences in spatial learning and memory that are not modified by the chronic treatment with cocaine. Moreover, hippocampal spine density is cocaine-modulated in both strains of rats. In conclusion, cocaine induces similar changes in hippocampal neurons morphology that are not related to genetic differences in spatial learning in the RAM protocol used here.     

Rotation of Water in the Morris Water Maze Interferes with Path Integration Mechanisms of Place Navigation

The idea that place navigation in the Morris water maze is implemented by path integration between locations determined by landmark sighting was investigated in a 200-cm-diameter pool in which circular (7.2°/s) motion of water could be induced by tangentially arranged water jets. The rats were trained at 8 trials per day to navigate to an erectable platform which was raised after the rat had spent a criterion time in the target annulus (30 cm in diameter) in the midpoint of the NW quadrant. Asymptotic escape latency of 7 s was reached after 9 days in moving water (n= 8) and after 6 days in stationary water (n= 8). The group overtrained for 13 days in stable water performed well even after it was transferred to moving water. Changing the sense of rotation of water from counterclockwise to clockwise did not affect the asymptotic performance. The above findings show that overtrained rats rely on landmark sighting rather than on path integration. The influence of water movement reappeared when place navigation to a new target (SW) was examined in alternating 2-s periods of light (L) and darkness (D). On the first day, the latencies were 15.2 ± 1.2 and 22.8 ± 1.9 s in stable and moving water, respectively, but dropped to 10 s on the following day. The tracks generated in the L period were more tortuous than those generated in the D period and this difference was more pronounced in moving than in stable water. It is concluded that path integration mechanisms supporting navigation during intervals of darkness are impaired in moving water but that this impairment disappears in overtrained animals.     

Intra-amygdala anxiogenic drug infusion prior to retrieval biases rats towards the use of habit memory

In a dual-solution plus-maze task that can be acquired using either hippocampus-dependent "cognitive/place" learning or dorsal striatal-dependent "habit/response" learning, pre-acquisition peripheral or intra-basolateral amygdala (BLA) injections of anxiogenic drugs result in the predominant use of response learning. The present experiments examined the effect of anxiogenic drug treatment on the relative use of multiple memory systems when administered prior to memory retrieval. Adult male Long-Evans rats were trained for two days (6 trials/day, 30s ITI) in a dual-solution plus-maze task to swim from the same start point (south) to an escape platform that was located in a consistent goal arm (west). On day three, prior to a memory retrieval probe trial from a novel start point (north), rats received a peripheral (0.03, 0.1 or 0.3 mg/kg), or intra-BLA (0.1 microg/0.5 microl) injection of the anxiogenic alpha(2)-adrenoreceptor antagonist RS 79948-197, or saline. Relative to saline controls, rats receiving either peripheral or intra-BLA infusions of RS 79948-197 predominantly displayed response learning on the probe trial. In an additional experiment peripheral (0.1 mg/kg) or intra-BLA (0.1 microg) drug injections administered prior to both acquisition and retrieval also resulted in the predominant use of response learning. The findings indicate that (1) similar to acquisition, peripheral injection of an anxiogenic drug prior to memory retrieval biases rats towards the use of habit/response memory, (2) intra-BLA infusions of an anxiogenic drug is sufficient to produce this modulatory effect of emotional state on memory retrieval, and (3) state-dependency does not appear to play a role in the effects of anxiogenic drug treatment on multiple memory system use. The findings may have implications for understanding the interaction between brain function, emotion, and the relative use of multiple memory systems in human psychopathology.     

Is there stimulant sensitivity in children?

It has been suggested that exposure to stimulants alters the dopamine system and thus enhances sensitivity to stimulants and possibly other drugs. Sensitization has been induced experimentally in animals, especially in rats, and has been shown to be long-lasting. In addition, cross-sensitization across different compounds has been demonstrated. The animal data have raised concern that exposure to methylphenidate in childhood may enhance the risk for later abuse of stimulants and other drugs. We review the evidence bearing on sensitization in children treated with stimulants and followed into adulthood. None of four clinic-based studies found an excess of drug abuse in children previously treated with stimulants. A school-based longitudinal study obtained a relationship between early stimulant treatment and later drug use, without controlling for dinical confounds. The single prospective-controlled study of children who received placebo or methylphenidate does not support the sensitization hypothesis.