Repeated exposure to cocaine increases the density of dendritic spines on medium spiny neurons in the nucleus accumbens (Acb) and pyramidal cells in the medial prefrontal cortex (mPFC). To determine if this is associated with the development of psychomotor sensitization, rats were given daily i.p. injections of 15 mg/kg of cocaine (or saline) for 8 days, either in their home cage (which failed to induce significant psychomotor sensitization) or in a distinct and relatively novel test cage (which induced robust psychomotor sensitization). Their brains were obtained 2 weeks after the last injection and processed for Golgi-Cox staining. In the Acb core (AcbC) cocaine treatment increased spine density only in the group that developed psychomotor sensitization (i.e. in the Novel but not Home group), and there was a significant positive correlation between the degree of psychomotor sensitization and spine density. In the Acb shell (AcbS) cocaine increased spine density to the same extent in both groups; i.e. independent of psychomotor sensitization. In the mPFC cocaine increased spine density in both groups, but to a significantly greater extent in the Novel group. Furthermore, when rats were treated at Home with a higher dose of cocaine (30 mg/kg), cocaine now induced psychomotor sensitization in this context, and also increased spine density in the AcbC. Thus, the context in which cocaine is experienced influences its ability to reorganize patterns of synaptic connectivity in the Acb and mPFC, and the induction of psychomotor sensitization is associated with structural plasticity in the AcbC and mPFC, but not the AcbS.

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In earlier studies it was found that glutamatergic transmission within the nucleus accumbens septi is involved in the performance of a learned visual shape discrimination in pigeons. This study examines what effects several kinds of glutamate and dopamine antagonists have on the same task. Pigeons were trained with the relevant discrimination, bilaterally implanted with cannulas into the nucleus accumbens and tested after various transmission blockers had been administered intracerebrally. SCH-23390, a D1 dopamine antagonist, at the dose used, had no effect, and Spiperone, a D2-dopamine and 5HT2a-serotonine antagonist, significantly decreased the error repeat trials. CNQX, a non-NMDA glutamate receptor antagonist, and Cycloleucine, an antagonist of the glycine allosteric site of NMDA receptors, had no effect. CGS-19755, a selective competitive NMDA antagonist, significantly impaired performance by significantly decreasing the percent correct trials and increasing the error repeat trials. CPPG, a II/III metabotropic glutamate antagonist, remarkably improved performance. MMPG, a III/II metabotropic glutamate antagonist, at the dose used, did not have any significant effect. The preparation employed may be a useful animal model of perceptual disturbances in schizophrenia.

A typical nonverbal transitive inference task (TI) consists of several overlapping discriminations (A+ B-, B+ C-, C+ D-, D+ E-, where letters indicate stimuli and pluses and minuses denote reinforcement and nonreinforcement). A choice of stimulus B in a novel pair BD is interpreted as indicative of a TI (if B > C and C > D, then B > D). Although hippocampus has been implicated in nonverbal TI, it is not clear whether it simply maintains memory of associative values or stores an ordered representation of stimuli. We investigated the effect of hippocampal lesion on TI in pigeons while controlling reinforcement history so that reliance on associative values would lead to a choice of a stimulus D in the pair BD instead of a choice of a stimulus B expected by inferential mechanisms. Prior to the lesion, some of the pigeons (relational group; n = 4) have selected B over D indicating TI, while other birds (associative group; n = 6) chose D over B suggesting reliance on associative values. Hippocampal lesion had no effect on postlesion performance in associative group. In contrast, the relational group that preferred stimulus B in a pair BD before lesion showed a near-chance performance after the lesion. Our results demonstrate that hippocampus may be involved in creating a representation of an ordered series of the stimuli instead of maintaining reinforcement history of each stimulus. In addition, we provide a behavioral procedure suitable for dissociating different behavioral strategies used to solving TI task. Finally, we show for the first time the involvement of avian hippocampus in the task that is not explicitly spatial in nature. These results further confirm the notion that avian hippocampus is functionally analogous to mammalian hippocampus despite the significant differences in their anatomy.

Upon systemic administration of apomorphine, a potent dopamine agonist, pigeons show a bout of pecking behaviour. When the drug is repeatedly administered a sensitization takes place that is associated with pronounced discrimination learning. Here we show that intra-cerebral injections of apomorphine in the periphery of the nucleus accumbens of pigeons also elicit pecking. We additionally show that injections of 5-amino-phosphonohepatnoic acid, a NMDA-glutamate receptor blocker, into the Acc impairs the performance of a learned visual discrimination incorporating pecking as a choice response. We conclude that, as it is the case in mammals, the control mechanisms of learned sensory-motor behaviour in birds involves dopaminergic and glutamatergic synaptic transmission within the nucleus accumbens area.