It has been suggested that dopamine autoreceptor subsensitivity may play a role in cocaine‐induced behavioral sensitization. In order to evaluate this hypothesis, we administered cocaine to rats daily (15 mg/kg ip × 2 days, 30 mg/kg ip × 5 days) and then monitored nucleus accumbens dopamine during the local administration (through the dialysis probe) of the D2/D3 agonist, quinpirole (0, 0.1, 1, and 10 μM). Our results indicate that, relative to saline‐pretreated control animals, repeated cocaine administration impaired the ability of quinpirole to decrease extracellular dopamine 1–2 days after the last drug injection. However, quinpirole was equipotent at reducing accumbal dopamine in cocaine‐ and saline‐treated animals following a 21–22 day withdrawal period. These results demonstrate that repeated cocaine produces a short duration functional tolerance in the capacity of autoreceptor stimulation to inhibit accumbal dopamine release. © 1995 Wiley‐Liss, Inc.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Behavioral sensitization