Behavioral conditioned responses across multiple conditioning/testing trials elicited by lithium- and amphetamine-paired flavors

The present experiment measured the pattern of conditioned responses across 10 conditioning/testing trials which were elicited by an intraoral presentation of either a lithium- or an amphetamine-paired flavor. A nonspecific conditioned response pattern of suppressed limb flicking after five conditioning trials and of suppressed scratching after six conditioning trials was supported by both drugs. Lithium-specific increased activity level after one conditioning trial and chin rubbing after two conditioning trials were observed across conditioning/testing days. The lithium-specific conditioned responses were not the result of a stronger flavor aversion, because both lithium and amphetamine produced equivalent flavor avoidance responses across the 10 conditioning/testing trials. The results support previous research which suggests that flavor aversions produced by lithium and amphetamine are produced by different unconditioned response mechanisms.     

Nonconsummatory and consummatory behavioral CRs elicited by lithium- and amphetamine-paired flavors

Various behavioral CRs elicited by saccharin solution previously paired with either lithium or amphetamine were measured in a series of four experiments. With one conditioning trial, lithium (Experiment 1), but not amphetamine (Experiment 2), produced nonconsummatory behavioral evidence of conditioning in the form of chin-rub CRs; both drugs, however, produced strong flavor aversions. With 3 conditioning trials, lithium- and amphetamine-paired flavors elicited a pattern of agitated activity, characterized by increased general activity, rearing duration, and body temperature, when the flavor was forcibly presented through an intraoral cannula (Experiment 3). When the flavor was presented in a single-bottle test (Experiment 4), 3 conditioning trials produced a similar pattern of agitated activity characterized by increased general activity, rearing (duration and frequency), stretching (duration and frequency), and limb flicking. Although both drugs supported the pattern of increased agitation-related CRs, only the lithium-paired flavors elicited chin-rub CRs (Experiments 1, 3, and 4). The difference between the drug conditions was not the result of a greater saccharin aversion in the lithium-conditioned group than in the amphetamine-conditioned group (Experiment 4). The results are related to findings that suggest that flavor aversions are mediated by a shift in the hedonic properties of the drug-paired flavors.     

Transfer of avoidance responding to a sensory preconditioned cue: Evidence for the role of S-S and R-S knowledge in avoidance learning

In avoidance learning studies, a warning signal (Sd) is directly paired with an aversive unconditioned stimulus (US) unless a particular response is performed. Research by Augustson and Dougher (1997) demonstrated that not only warning signals but also stimuli that are indirectly paired with the aversive event are capable of affecting the avoidance response. In the present study, we extended these results by incorporating a sensory preconditioning paradigm in an avoidance learning procedure. Sensory preconditioning training influenced the selection of avoidance responses in the presence of warning signals that were never paired directly with the aversive events. Moreover, results suggest that the selection of the avoidance responses was based on an integration of knowledge about the relation between the Sd and the US (S-S knowledge) and knowledge about the relation between the avoidance response and the US (R-S knowledge). As the expectancy-based theory of Lovibond (2006) is the only theory of avoidance that incorporates both knowledge structures, the results provide unique support for this theory.     

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.     

Modification of the punishing effects of psychoactive drugs in rats by previous drug experience.

In Experiment 1, it was shown that chronic prior exposure to amphetamine attenuated the conditioned avoidance of saccharin that was produced by both amphetamine and morphine during gustatory conditioning trials; the relationship between morphine and amphetamine was somewhat anomalous because of their pharmacological dissimilarity. The relationship was also asymmetrical, since in Experiment 2, chronic prior exposure to morphine failed to mitigate avoidance conditioning by amphetamine but was effective in attenuating conditioning by morphine itself. In a third experiment, it was found that prior treatment with chlordiazepoxide attenuated saccharin avoidance conditioned by chlordiazepoxide but not by amphetamine or morphine. The findings were related to Parker, Failor, and Weidman's hypothesis, based on findings with morphine, concerning the development of conditioned preferences for substances associated with the repletion of artificially induced biological needs. It was suggested that the findings were best interpreted as a reflection of drug tolerance rather than conditioned preference.     

Amphetamine, conditioned stimulus, and nondebilitating preshock effects on activity and avoidance: further evidence for interactions between associative and nonassociative changes

A literature survey and preliminary experiments with rats on the consequences of shock preexposure on subsequent activity and escape or avoidance showed the need for further work on the interactions between nondebilitating preshock and various test and treatment factors. The two main experiments used 16 preexposure conditions, namely, presence or absence of unavoidable punishment (36 shocks of 2.5 mA and 5 sec subdivided in three daily sessions), a light CS, a central partition in the shuttle-box, and dl-amphetamine sulfate (1 mg/kg ip 15 min before each session). In both experiments the four factors studied exerted more than additive effects on activity in preexposure sessions, leading to a very high frequency of crossing in the CS-shock-no-partition-drug condition. Upon retesting for activity (Experiment 1) suppression of locomotion by prior shock was less marked in animals preexposed to CS-US pairings in the absence of partition, while proactive amphetamine effects consisted mainly of a progressive increase of activity over successive retest sessions in the groups not preshocked. Upon retesting for light-cued, two-way avoidance acquisition (Experiment 2) the groups preexposed to US only were mostly retarded, while those preexposed to paired CS and US were mostly facilitated. Other changes, including drug pretreatment consequences, were negligible or unsystematic, but in general the data showed that the effects of various preexposure conditions on activity could not account for those on avoidance. Overall, it appears that the interactions between nondebilitating preshock and other test and treatment factors can be further exploited to clarify the respective roles of various associative and nonassociative mechanisms in modulation of activity and adaptive responding in aversive situations.     

Conditioned activity and the interaction of amphetamine experience with morphine's activity effects

This experiment assessed the transfer effect of Pavlovian conditioning with d-amphetamine sulfate (1 mg/kg) on morphine's activity effects. Prior experience with amphetamine resulted in higher levels of activity when challenged with morphine (10 and 20 mg/kg). This interactive effect of amphetamine, however, was present only in those animals who had experienced amphetamine paired with the activity test situation. Animals who had received equivalent doses of amphetamine unpaired with the testing environment did not differ from drug-naive control animals. Analysis of predrug activity levels revealed a conditioned activity response in paired animals compared to the controls. These findings suggest that the response interaction between drug conditioned responses and drug unconditioned responses is an important determinant of cross-drug effects between drugs of different pharmacological classes.     

Active avoidance conditioning in zebrafish (Danio rerio)

The zebrafish represents a potentially useful organism for studying genes involved in learning and memory function in vertebrates, because a number of genetic techniques in zebrafish have been developed to produce a wide variety of genetic mutants. While zebrafish mutants are being developed, behavioral studies on learning and memory function in zebrafish are in urgent need. The present study investigated active avoidance conditioning in normal zebrafish. Zebrafish were trained to swim from a lighted (CS) compartment to a dark compartment to avoid an electrical body shock (US) in a shuttle-box that consisted of a water-filled tank separated by an opaque barrier into two equal compartments. By varying the number of trials per training session and the duration of the intertrial interval, Experiments 1 and 2 showed that, with the CS, US, and intertrial interval being 12s, zebrafish learned avoidance responses within a training session consisting of 30 trials and retained the avoidance responses. Experiment 3 showed that zebrafish learned avoidance responses following the association between the CS of light and the US of shock in the avoidance conditioning paradigm. Using the avoidance conditioning paradigm, Experiment 4 investigated the amnestic effects of N-methyl-D-aspartate receptor antagonist MK-801 and nitric oxide synthase inhibitor L-NAME in zebrafish. Experiment 4 showed that post-training injection of L-NAME significantly impaired retention of avoidance responses while MK-801 did not, confirming previous results with other vertebrates. The results of the present study suggest the similar involvements of neurochemicals in learning and memory among vertebrates. Thus, future studies with zebrafish mutants may identify genes involved in learning and memory in vertebrates.     

Taste Aversion Learning Based on Swimming and Lithium Chloride Injection in Rats: Implications From Cross-familiarization Tests and Stimulus Selectivity1

In rats, swimming causes avoidance of the taste solution consumed immediately before the swimming. Several lines of research have shown that this taste avoidance reflects Pavlovian conditioned aversion based on correlations between the taste and swimming-induced nausea. The present research compared swimming-based taste aversion learning (TAL) with conventional TAL based on nausea-inducing lithium chloride (LiCl). By exploiting cross-familiarization techniques, Experiments 1A and 1B suggested that different physiological states are induced by swimming and LiCl. This claim was supported by Experiment 2, which reports stimulus selectivity in saccharin and sucrose aversions based on swimming and LiCl.     

When do motor behaviors (mis)match affective stimuli? An evaluative coding view of approach and avoidance reactions

Affective-mapping effects between affective stimuli and lever movements are critically dependent upon the evaluative meaning of the response labels that are used in the task instructions. In Experiments 1 and 2, affective-mapping effects predicted by specific-muscle-activation and distance-regulation accounts were replicated when the standard response labels towards and away were used but were reversed when identical lever movements were labeled downwards and upwards. In Experiment 3, affective-mapping effects were produced with affectively labeled right and left lever movements that are intrinsically unrelated to approach and avoidance. Experiments 4 and 5 revealed that affective-mapping effects are not mediated by memory retrieval processes and depend on the execution of affectively coded responses. The results support the assumption that evaluative implications of action instructions assign affective codes to motor responses on a representational level that interact with stimulus evaluations on a response selection stage.     

Immobility as an avoidance response, and its disruption by drugs

Much of the available literature on avoidance behavior is based on responses which require the animal to run, lever-press, or to make some active response to avoid noxious stimulation. The purpose of Experiment I reported in this paper was to determine whether animals can learn to sit or stand motionless in order to escape or avoid electric shock. Five experimental rats were given escape-avoidance training, while five yoked control animals received electric shocks without any response-related contingency. It was shown that an immobility avoidance response, as distinct from the unconditioned “freezing” response to shock, can be trained. The results of Experiment II (30 rats) revealed that this response is more readily acquired at higher shock intensities than at lower ones, provided escape by jumping is prevented at the high shock intensities. The effects of six doses of each of three drugs on the immobility avoidance response were studied in Experiment III (13 rats). Methylphenidate, chlorpromazine, and imipramine all produced a decrement in the immobility response, but the pattern and amount of the effects of the three drugs were quite different, one from the other. The implications of these findings for a general theory of avoidance behavior and for drug screening are discussed.     

Evidence against an occasion setting account of avoidance learning

Earlier studies on human avoidance learning showed that an avoidance response reduces the expectancy that a warning stimulus (WS) will be followed by an unconditioned stimulus (US). This modulation can transfer to WSs with which the avoidance response did not occur in the past. Recent studies suggest that transfer of modulation is selective in that it is stronger for WSs that previously went together with other avoidance responses than for WSs that never went together with an avoidance response. This finding has been interpreted as providing unique support for an occasion setting account of avoidance learning. We put forward alternative explanations of selective transfer of modulation in terms of the rate with which a WS was reinforced in the absence an avoidance response. In support of the alternative explanations, we found that transfer of modulation depended not on whether a WS previously went together with another avoidance response but on the rate with which the WS was reinforced in the past. We conclude that selective transfer of modulation in avoidance learning does not provide (unique) support for the occasion setting account. Our findings are in line with a revised expectancy model of avoidance learning.     

Interference with ingestional aversion learning produced by preexposure to the unconditioned stimulus: Associative and nonassociative aspects

Preconditioning exposure to a lithium chloride unconditioned stimulus (US) interferes with the subsequent conditioning of a taste aversion. Multiple US preexposures produce a long-lasting or durable interference with aversion learning, whereas a single US exposure produces a transient interference effect. The present experiments demonstrate that the durable US preexposure effect is substantially reduced if the method of drug treatment (infusion versus injection of the drug into the peritoneal cavity) or the spatial cues present during drug treatment (home cage versus a distinctive environment) are changed between the preexposure and taste conditioning phases of the experiment. In contrast, these manipulations do not attenuate the proximal/transient US preexposure effect. These findings indicate that different mechanisms are responsible for the two US preexposure effects. The results are consistent with previous suggestions that the durable effects of lithium preexposure are due to associative interference produced by the exteroceptive stimuli that accompany drug administrations and indicate that the proximal/transient US preexposure effect is mediated by nonassociative mechanisms.     

Dissociation between conditioned emotional response and extended avoidance performance

The present experiments examined the dissociation between the strength of a shuttlebox avoidance response (AR) and one index of fear of the avoidance CS. Avoidance response strength was indexed by resistance to extinction of the AR and by changes in response latency, and fear of the CS was indexed by the conditioned emotional response (CER) technique. Experiments 1, 2A, and 3A all found that rats trained to a criterion of 27 consecutive avoidance responses (CARs) showed response strength comparable or superior to rats trained to a criterion of 9 CARs. Experiments 2B and 3A demonstrated that rats trained to 27 CARs showed less suppression of bar pressing during the avoidance CS (less CER) than rats trained to 9 CARs. Experiment 3A also found that, when extinguished in the shuttlebox to a moderate criterion (5 consecutive trials without a response) before CER testing, rats trained to 9 CARs showed some, although not complete, loss of CER, whereas rats trained to 27 CARs showed no loss of CER. In Experiment 3B rats that took 1 vs 2 days to reach a criterion of 27 CARs were compared for their AR strength and for their CER. Although rats taking 2 days to reach criterion showed somewhat greater resistance to extinction of the AR than rats reaching criterion in 1 day, this variable had no apparent effect on the CER. Implications of the present results for current theories of avoidance learning are discussed.     

Amphetamine effects on unconditional and conditional instrumental responses with alimentary and social rewards in dogs

The effect of amphetamine dose (0.5 mg per 1 kg) on conditional and unconditional responses based on alimentary and social motivation was investigated in two groups of dogs. Amphetamine resulted in a significant decrease of conditional instrumental responses (CRs) in both groups but did not attenuate significantly the dogs’ need for food or petting. On the contrary, the drug drastically increased the dogs’ need for petting, and its anorectic effect was mild. The deteriorating effect of amphetamine on mnemonic processes and its facilitatory effect on behaviors directed to get more than the usual amount of pleasant tactile stimulation might underlie the behavioral changes described in this study.     

Androgens' performance-enhancing effects in the inhibitory avoidance and water maze tasks may involve actions at intracellular androgen receptors in the dorsal hippocampus

Androgens can have performance-enhancing effects in some cognitive tasks, but the mechanism of these effects has not been established. Experiments examined whether androgens' actions to bind to intracellular androgen receptors (ARs) in the hippocampus are necessary to enhance cognitive performance in the inhibitory avoidance and water maze tasks. If androgens' binding at ARs are essential, then blocking them through intrahippocampal administration of flutamide, an AR receptor antagonist, should attenuate androgens' performance-enhancing effects in the inhibitory avoidance and water maze tasks. In Experiments 1 and 2, flutamide was administered through intrahippocampal inserts to intact male rats immediately pre- and post-training in the inhibitory avoidance and water maze tasks. Both pre- and post-training administration of flutamide to the dorsal hippocampus, but not missed sites, produced significantly poorer performance in the inhibitory avoidance and water maze tasks, without influencing control measures such as flinch/jump threshold or swim speed. In Experiment 3, flutamide administration to the hippocampus was delayed two hours following training in the inhibitory avoidance and water maze tasks. There was no significant effect of delayed administration of flutamide on performance in either of these tasks. Together, these findings suggest that blocking ARs in the dorsal hippocampus with flutamide administration immediately pre- or post-training can produce decrements in cognitive performance, which implies that androgens' performance-enhancing effects may occur, in part, through binding at intracellular androgen receptors in the dorsal hippocampus.     

Effect of changing the unconditioned stimulus on appetitive blocking

In four experiments we examined the effects of changing the unconditioned stimulus (US) on appetitive blocking. In Experiments 1A, 1B, and 2 we established that substituting food for water, or water for food, in the compound stage did not attenuate blocking relative to groups that received the same US throughout conditioning. Experiment 3 showed that satiation with the US used prior to compound conditioning with a different US does not affect blocking. Experiment 4 revealed that changing the location of US delivery, as well as the quality of the US, also leaves blocking unaffected. It is suggested that these results demonstrate that blocking occurs, provided that there is no change in the affective properties of the US.     

Acoustic and semantic similarity effects on repetition avoidance in produced sequences

The question of whether repetition avoidance in sequential response production depends on the phonetic or the semantic encoding of previous responses was investigated by varying the acoustic and semantic similarity among the response alternatives. The results indicated that acoustic similarity affected repetition avoidance with six alternative words and a production rate of one per second, but not with four alternative letters and a rate of one per 2 sac. Semantic similarity between words was also studied, and was not seen to affect repetition avoidance. Results were explained by means of a model in which comparisons between a memory set of admissible responses and a memory set of recent responses are made at a phonetic level of response representation.     

Minimal information to determine affine shape equivalence

Participants judged the affine equivalence of 2 simultaneously presented 4-point patterns. Performance level (d') varied between 1.5 and 2.7, depending on the information available for solving the correspondence problem (insufficient in Experiment 1a, superfluous in Experiment 1b, and minimal in Experiments 1c, 2a, 2b) and on the exposure time (unlimited in Experiments 1 and 2a and 500 ms in Experiment 2b), but it did not vary much with the complexity of the affine transformation (rotation and slant in Experiment 1 and same plus tilt in Experiment 2). Performance in Experiment 3 was lower with 3-point patterns than with 4-point patterns, whereas blocking the trials according to the affine transformation parameters had little effect. Determining affine shape equivalence with minimal-information displays is based on a fast assessment of qualitatively or quasi-invariant properties such as convexity/ concavity, parallelism, and collinearity.     

Growth hormone response to different consecutive stress stimuli in healthy men: is there any difference?

The contribution of growth hormone (GH), released during acute and repeated stressful situations, to the development of stress-related disorders is often neglected. We have hypothesized that the modulation of the GH response to sequential stress exposure in humans depends mainly on the nature of the stressor. To test this hypothesis, we compared GH responses to different stressful situations, namely aerobic exercise, hypoglycemia and hyperthermia, which were applied in two sequential sessions separated by 80-150 min. In addition, administration of the dopaminergic drug apomorphine was used as a pharmacological stimulus. GH responses to submaximal exercise (bicycle ergometer, increasing work loads of 1.5, 2.0 and 2.5 W/kg, total duration 20 min) and hyperthermia in a sauna (80 degrees C, 30 min) were prevented when preceded by the same stress stimulus. Hypoglycemia induced by insulin (0.1 IU/kg intravenously) resulted in a significant GH response also during the second of the two consecutive insulin tests, though the response was reduced. Administration of apomorphine (0.75 mg subcutaneously) or insulin prevented the increase in GH release in response to a sequential bolus of apomorphine, while hypoglycemia induced a significant elevation in GH levels even if applied after a previous treatment with apomorphine. In conclusion, the feedback inhibition of the GH response to a sequential stress stimulus depends on the stimulus used. Unlike in the case of exercise and hyperthermia, mechanisms involved in the stress response to hypoglycemia appear to overcome the usual feedback mechanisms and to re-induce the GH response when applied after another stimulus.