ENHANCED REWARD-RELATED RESPONDING FOLLOWING CHOLERA-TOXIN INFUSION INTO THE NUCLEUS-ACCUMBENS

In recent years, considerable focus has been directed to understanding how drugs of abuse affect neuronal function at the molecular level. F or example, repeated administration of stimulants or opiates can induc e long-lasting alterations in gene expression, transcription factors, and signal transduction pathways. Our laboratory previously showed tha t intraaccumbens infusion of cholera toxin (CTX), which alters the G(S ) protein such that production of cyclic Adenosine Monophosphate (AMP) is upregulated, causes pronounced, long-lasting motor activation and sensitization to stimulants. In the present experiments, the effect of intraaccumbens infusion of cholera toxin on reward-related responding was investigated. The conditioned reinforcement (CR) paradigm was emp loyed, which measures an animal's instrumental response to obtain pres entation of a stimulus previously paired with a primary reward. When t his stimulus supports acquisition of a new operant response (lever-pre ssing), it is termed a conditioned reinforcer (CR). In the first exper iment, the effects of bilateral intraaccumbens infusion of CTX (100 ng /l mu l) were examined on previously-established responding. CTX treat ment resulted in enhanced responding for the CR. This enhancement deve loped over several days and reached its peak 3 days following infusion . In the second experiment, the influence of CTX was examined on acqui sition of responding for the CR. The group treated with CTX (100 ng) d iscriminated between the CR and control (NCR) lever earlier than the v ehicle-infused group, and showed greater levels of responding on the C R lever. In the third experiment, it was determined that infusion of C TX (300 ng bilaterally) into the anterior dorsal striatum did not affe ct levels of responding, although a later test with cocaine in these a nimals (25 mg/kg, intraperitoneally) (i.p.) indicated that they were c apable of potentiated responding. These data are interpreted as eviden ce that the Gs protein-cyclic AMP second messenger system within the n ucleus accumbens is directly involved in reward-related behavior. (C) 1997 WILEY-LISS, INC.