Repeated post- or presession cocaine administration: roles of dose and fixed-ratio schedule

Effects of repeated administration of cocaine to animals behaving under operant contingencies have depended on when the drug is given. Moderate doses given presession have generally led to a decrease in the drug's effect, an outcome usually referred to as tolerance. When these same doses have been given after sessions, the usual result has been no change or an increase in the drug's effects, with the latter usually referred to as sensitization. In the present study, repeated postsession administration of a relatively small dose of cocaine (3.0 or 5.6 mg/kg) to pigeons responding under a multiple fixed-ratio 5, fixed-ratio 100 schedule of food presentation generally resulted in tolerance to the rate-decreasing effects of the drug. When the same dose was given before sessions, little additional tolerance was observed, although some subjects showed further tolerance in the small-ratio component. A regimen of repeated postsession injection of larger (10.0-23.0 mg/kg) doses suppressed key pecking during the session; responding resumed following discontinuation of postsession administrations. Effects of postsession administration of cocaine, therefore, depended on the dose, with smaller doses leading to tolerance and larger ones to suppression of behavior during the session. Effects of postsession drug administration of either small or large doses were not related to whether effects of postsession drug were experienced mainly in the operant test chamber or in the pigeon's home cage. The results with large postsession doses are compatible with a view that the drug acted as a Pavlovian unconditional stimulus, with the session-related stimuli acting as a long-duration Pavlovian conditional stimulus. Tolerance following postsession administration of the smaller doses challenges the view that it depended on experiencing the drug's effects while the arranged reinforcement contingencies were in effect.     

Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning

Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400 microg/ml) in their drinking water (days 1-21), a manipulation that was previously shown to cause hippocampal CA3 dendritic retraction. Subsequently, rats were adapted to the fear conditioning chamber (day 22), then trained (day 23), and tested for conditioned fear to context and tone (day 25). Training consisted of two tone (20s) and footshock (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 microl/side), a GABAergic agonist, was microinfused to temporarily inactivate the BLA during training. Rats given chronic corticosterone showed enhanced freezing to context, but not tone, compared to vehicle-supplemented rats. Moreover, BLA inactivation impaired contextual and tone conditioning, regardless of corticosterone treatment. In Experiment 2, RU486 (0, 0.3, and 3.0 ng/0.2 microl/side) was infused on training day to antagonize glucocorticoid receptors in the BLA. Corticosterone treatment enhanced fear conditioning to context and tone when analyzed together, but not separately. Moreover, RU486 (3.0 ng/side) selectively exacerbated freezing to context in chronic corticosterone-exposed rats only, but failed to alter tone conditioning. Serum corticosterone levels were negatively correlated with contextual, not tone, conditioning. Altogether, these suggest that chronic corticosterone influences fear conditioning differently than chronic stress as shown previously. Moreover, chronic exposure to corticosteroids alters BLA functioning in a non-linear fashion and that contextual conditioning is influenced more than tone conditioning by chronic corticosterone and BLA glucocorticoid receptor stimulation.     

Function transformation without reinforcement

In studies of function transformation, participants initially are taught to match stimuli in the presence of a contextual cue, X; the stimuli to be matched bear some formal relation to each other, for example, a relation of opposition or difference. In a second phase, the participants are taught to match arbitrary stimuli (say, A and B) in the presence of X. In a final test, A often displays behavioral functions that differ from those of B, and can be predicted from the nature of the relation associated with X in the initial training phase. Here we report function-transformation effects in the absence of selection responses and of their reinforcers. In three experiments with college students, exposure to relations of difference or identity modified the responses given to later stimuli. In Experiment 1, responses to a test stimulus A varied depending on preexposure to pairs of colors that were distinct from A but exemplified relations of difference or identity. In Experiment 2, a stimulus A acquired distinct functions, depending on its previous pairing with a contextual cue X that had itself been paired with identity or difference among colors. Experiment 3 confirmed the results of Experiment 2 with a modified design. Our data are consistent with the notion that relations of identity or difference can serve as stimuli for Pavlovian processes, and, in compound with other cues, produce apparent function-transformation effects.     

Response-restriction analysis: II. Alteration of activity preferences

We used response-restriction (RR) assessments to identify the preferences of 7 individuals with mental retardation for a variety of vocational and leisure activities. We subsequently increased their engagement in nonpreferred activities using several procedures: response restriction per se versus a Premack-type contingency (Study 1), supplemental reinforcement for engagement in target activities (Study 2), and noncontingent pairing of reinforcers with nonpreferred activities (Study 3). Results indicated that preferences are not immutable and can be altered through a variety of relatively benign interventions and that the results of RR assessments may be helpful in determining which types of procedures may be most effective on an individual basis.     

Instrumental learning in hyperdopaminergic mice

In two experiments we investigated the effects of elevated dopaminergic tone on instrumental learning and performance using dopamine transporter knockdown (DAT KD) mice. In Experiment 1, we showed that both DAT KD mice and wild-type controls were similarly sensitive to outcome devaluation induced by sensory specific satiety, indicating normal action-outcome learning in both groups. In Experiment 2, we used a Pavlovian-to-instrumental transfer procedure to assess the potentiation of instrumental responding by Pavlovian conditional stimuli (CS). Although during the Pavlovian training phase the DAT KD mice entered the food magazine more frequently in the absence of the CS, when tested later both groups showed outcome-selective PIT. These results suggest that the elevated dopaminergic tone reduced the selectivity of stimulus control over conditioned behavior, but did not affect instrumental learning.     

Return of fear in a human differential conditioning paradigm caused by a return to the original acquistion context

In a differential human fear conditioning paradigm evidence for ABA-renewal was obtained manipulating the lighting in the experimental room. During acquisition in either a dark or illuminated room, one neutral slide was sometimes paired with a loud aversive noise whereas another slide was not. Subsequently, extinction took place in the opposite lighting context. When afterwards the participants were tested again in the original acquisition context, measurements revealed a recovery of the conditioned electrodermal response and an increase in the retrospective verbal US-expectancy ratings. No response recovery was obtained in an AAA-group that received acquisition, extinction and test trials in one and the same context. Several theoretical explanations for this type of return of fear as well as implications for clinical practice are discussed.     

Reinstatement of fear responses in human aversive conditioning

The treatment of choice for a number of anxiety disorders is exposure therapy. However, successful reduction of fear through exposure is sometimes followed by a (partial) return of symptoms of fear (return of fear, ROF; Clin. Psychol. Rev. 9 (1989) 147). Several possible learning mechanisms have been suggested to explain ROF (e.g. mechanisms related to spontaneous recovery, renewal, reacquisition and reinstatement). The present study focuses on reinstatement, which refers to the observation that mere US-only presentations can 'reinstate' previously extinguished fear responses. Although animal research has repeatedly demonstrated this phenomenon, little is known about fear reinstatement in humans. The present study employed a differential aversive conditioning procedure: after acquisition and a subsequent extinction procedure, a series of four unpredicted US-only trials was scheduled in the reinstatement group. The control group did not receive additional US presentations. A significant reinstatement effect was observed for US-expectancy ratings and fear ratings in the reinstatement group, but not in the control group. No differences were observed in a reaction time measure of resource allocation to the conditioned stimuli. These findings constitute a first demonstration of reinstatement of conditioned fear responses in humans. Implications for exposure treatment and suggestions for future research are discussed.     

Neuroscience and learning: lessons from studying the involvement of a region of cerebellar cortex in eyeblink classical conditioning

How the nervous system encodes learning and memory processes has interested researchers for 100 years. Over this span of time, a number of basic neuroscience methods has been developed to explore the relationship between learning and the brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and recording techniques. In this paper, we summarize how different research approaches can be employed to generate converging data that speak to how structures and systems in the brain are involved in simple associative learning. To accomplish this, we review data regarding the involvement of a particular region of cerebellar cortex (Larsell's lobule HVI) in the widely used paradigm of classical eyeblink conditioning. We also present new data on the role of lobule HVI in eyeblink conditioning generated by combining temporary brain inactivation and single-cell recording methods, an approach that looks promising for further advancing our understanding of relationships between brain and behavior.     

Limbic-striatal memory systems and drug addiction

Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits. Such habits evolve through a cascade of complex associative processes with Pavlovian and instrumental components that may depend on the integration and coordination of output from several somewhat independent neural systems of learning and memory, each contributing to behavioral performance. Data are reviewed that help to define the influences of conditioned Pavlovian stimuli on goal-directed behavior via sign-tracking, motivational arousal, and conditioned reinforcement. Such influences are mediated via defined corticolimbic-striatal systems converging on the ventral striatum and driving habit-based learning that may depend on the dorsal striatum. These systems include separate and overlapping influences from the amygdala, hippocampus, and cingulate and medial prefrontal cortex on drug-seeking as well as drug-taking behavior, including the propensity to relapse.     

Intrahippocampal scopolamine impairs both acquisition and consolidation of contextual fear conditioning

Lesions of the dorsal hippocampus have been shown to disrupt both the acquisition and the consolidation of memories associated with contextual fear (fear of the place of conditioning), but do not affect fear conditioning to discrete cues (e.g., a tone). Blockade of central muscarinic cholinergic receptor activation results in selective acquisition deficits of contextual fear conditioning, but reportedly has little effect on consolidation. Here we show for the first time that direct infusion of the muscarinic cholinergic receptor antagonist, scopolamine, into the dorsal hippocampus produces a dose-dependent deficit in both acquisition and consolidation of contextual fear conditioning, while having no impact on simple tone conditioning.