Repeated cocaine administration reduces 5-HT1A-mediated prolactin secretion in rats.

The prolactin and behavioral responses elicited by the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino]tetralin) were examined in male rats previously exposed to chronic cocaine (15 mg/kg, i.p., b.i.d., 7 days) or saline. After 42 h of withdrawal, cocaine-treated rats exhibited a reduced prolactin response to 8-OH-DPAT challenge (50 micrograms/kg, i.v.). A 5-fold higher dose of 8-OH-DPAT stimulated maximal prolactin secretion that was similar in cocaine- and saline-treated rats. Prior cocaine treatment had no effect on the 5-HT syndrome induced by 8-OH-DPAT. Our data agree with the findings of others and suggest that 5-HT1A receptors mediating neuroendocrine secretion become subsensitive after repeated cocaine administration.