Changes in response to a dopamine receptor antagonist in rats with escalating cocaine intake

Rationale and objectives. Prolonged access to cocaine self-administration (long access or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access or ShA). The present study tested the hypothesis that escalating use of cocaine is associated with chronic alterations in dopamine neurotransmission. Methods. After escalation of cocaine self-administration, ShA and LgA rats were challenged with different subcutaneous doses of cis-flupenthixol (10-270 mug/kg), a highly selective dopamine receptor antagonist. Results. In both groups, increasing doses of cis-flupenthixol first produced an increase in the number of cocaine injections and then a dramatic suppression of behavior. This biphasic dose-effect function-which replicates previous findings from this laboratory-was shifted to the left in LgA rats relative to ShA rats, thereby decreasing the threshold dose at which behavior was completely suppressed. Conclusions. These data support the hypothesis that alterations in dopamine neurotransmission contribute to escalation of cocaine self-administration.