Amphetamine Exposure Enhances Accumbal Responses to Reward-Predictive Stimuli in a Pavlovian Conditioned Approach Task

Abstract

Acute and repeated exposure to psychostimulants such as amphetamine enhances the effects of pavlovian conditioned stimuli on conditioned behavior. It is hypothesized that amphetamine facilitates conditioned stimulus (CS) effects by selectively enhancing accumbal neuronal responses to stimuli. To test this hypothesis, rats were trained to discriminate between two pavlovian stimuli. One stimulus (i.e., CSϩ) was paired with sucrose delivery [i.e., unconditioned stimulus (US)], and the other stimulus (i.e., CSϪ) was paired with the absence of sucrose. Animals developed a conditioned approach response that occurred during the CSϩ but not during the CSϪ. We tested the effect of different doses of amphetamine (0, 0.25, 0.5, or 1.0 mg/kg) on this conditioned approach behavior as well as on accumbal neuronal responses time locked to the CSϩ, the CSϪ, and the US. Acute amphetamine exposure increased conditioned approach behavior during the CSϩ, but not during the CSϪ. This change in behavior was associated with a selective increase in the magnitude of accumbal responses during the CSϩ. Repeated amphetamine administration followed by a drug-free period and reexposure did not affect the conditioned behavior, but increased accumbal responses to the CSϩ. These findings support the hypothesis that amphetamine exposure enhances behavioral responses to pavlovian conditioned stimuli by amplifying accumbal responses to those stimuli.

Amphetamine-induced enhancement of responding for conditioned reward in rats: interactions with repeated testing

“…These authors suggest that the CS may elicit responding by evoking not only an US representation but also a general appetitive representation. However, even though conditioned approach is enhanced by amphetamine (Wyvell and Berridge 2000;Wan and Peoples 2008), in the present study the CR response became less amphetamine-sensitive with repeated testing. Thus, our results extend and qualify these conclusions and suggest that a generalized appetitive representation is unlikely to maintain CR responding as extinction progresses.…”

“…Thus psychostimulants potentiate instrumental responding for natural rewards depending on the reinforcement schedule (Slawecki and Samson 1996), for brain stimulation reward (Gilliss et al 2002) and for reward-predicting stimuli (Sutton and Beninger 1999). Amphetamine selectively enhances nucleus accumbens neuronal firing to a conditioned stimulus (CS) paired with sucrose in a conditioned approach task (Wan and Peoples 2008). On the other hand, CS extinction and unexpected reward omission are associated with a suppression in dopamine cell firing (Schultz et al 1997;Pan et al 2008) and dopamine antagonism results in extinction-like behavior (Wise et al 1978).…”

Disentangling pleasure from incentive salience and learning signals in brain reward circuitry

“…An expectation from that reciprocal inhibition view would be that excitatory peaks of VP firing observed here might have corresponded to inhibitory pauses of NAc neurons, which have been suggested to signal reward (20,24,88,89). However, simultaneous excitations in NAc and VP (or simultaneous inhibitions) may also be possible (29,37,62,87,90), perhaps enabled by corelease of peptides such as dynorphin, enkephalin, or substance P to modulate the impact of GABA on postsynaptic neurons (5,6,32,87). Additionally, neurons of the NAc hotspot in the rostrodorsal medial shell may not project directly to neurons in the posterior VP hotspot recorded here but rather, to a more anterior site in VP and to lateral hypothalamus (7) from where interneurons might convey signals to posterior VP to contribute to functional interactions (37).…”

Effects of acute amphetamine exposure on two kinds of Pavlovian approach behavior

“…For example, acute AMP administration enhances performance of an instrumental response which was reinforced by presentation of a conditioned stimulus [12]. It has also been demonstrated that post-training administration of amphetamine enhanced consolidation of a Pavlovian conditioned approach response [14], and that acute amphetamine exposure enhances approach to a conditioned stimulus (CS+) associated with liquid sucrose reward but not approach of a stimulus not associated with such reward (CS−), and moreover that such enhanced responding to the CS+ was accompanied by increased magnitude of responding from neurons in nucleus accumbens [23]. These previous studies, however, have employed conditioning procedures where CS and US were delivered in the same location, and thus, sign- and goal- tracking behaviors would be indistinguishable from each other.…”

“…After subjects reached a stable level of performance, they were run in the task under five different doses of amphetamine and a saline control. Based on previous studies showing acute amphetamine enhances instrumental responding for conditioned reinforcement [12, 16], and approach of the CS [23], we hypothesized that AMP would enhance sign-tracking with increasing doses (i.e. decrease latency of the behavior, increase number of responses), and, to the extent that goal-tracking and sign-tracking are competing behaviors, decrease goal-tracking (i.e.…”