Withdrawal from continuous or intermittent cocaine: behavioral responsivity to 5-HT1 receptor agonists

Research on chronic cocaine administration indicates that both the dose and route of administration influences the effects of chronic cocaine. Rats were pretreated with 40 mg/kg/day cocaine for 14 days by either SC injections or osmotic minipumps. Rats were then withdrawn from the pretreatment regimen for 7 days and their behavior rated following injections of 5-hydroxytryptamine1A (5-HT1A) or 5-HT1B agonists. In Experiment 1, rats received 0- to 4.0-mg/kg IP injections of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT1A receptor agonist. In Experiment 2, rats received 0- to 16.0-mg/kg IP injections of 7-trifluoromethyl-4(4-methyl-1-piperazinyl)- pyrrolo[1,2a]quinoxaline (CGS 12066B), a selective 5-HT1B receptor agonist. The results of Experiment 1 indicated that rats receiving cocaine via osmotic minipumps exhibited marked 5-HT1A receptor subsensitivity. In contrast, rats receiving daily cocaine injections sometimes demonstrated evidence of 5-HT1A supersensitivity and sometimes demonstrated evidence of 5-HT1A normosensitivity. The results of Experiment 2 indicated there were no consistent differences between the pretreatment groups in the behavioral response to CGS 12066B, although there were significant differences at single, isolated time points. Overall, the results indicate that, at least in the present behavioral paradigm, the effects of chronic cocaine administration are mediated by changes in 5-HT1A receptor sensitivity but not by changes in 5-HT1B receptor sensitivity.