Functional Correlates Of 5-HT1A Receptor Activation After Exposure To Repeated Cocaine Administration In Rats

Abstract

It is well known that acute cocaine treatment has profound effects on serotonin (5-HT) neurons, but the consequences of chronic cocaine administration on 5-HT neurotransmission are not well studied. We used the 5-HT agonist 80H-DPAT as a probe to assess 5-HT1A receptor function in vivo in rats previously exposed to cocaine. Rats were treated with cocaine (15 mg/kg, ip) twice daily for one week. After 42 hr and 8 days of withdrawal, rats were challenged with 80H-DPAT (10-300 μg/kg, sc) or vehicle, and various endpoints were evaluated including: 5-HT synthesis in discrete brain regions, feeding, plasma prolactin, and the 5-HT behavioral syndrome. Prior cocaine exposure did not alter the 80H-DPAT-induced inhibition of 5-HT synthesis in any brain region examined. Although cocaine-treated rats exhibited higher basal rates of feeding, the hyperphagia produced by 80H-DPAT was comparable in cocaine- and saline-treated groups. The plasma prolactin response to 80H-DPAT was significantly blunted in cocaine-treated animals at 42 hr of withdrawal, and this effect was maintained at 8 days. Cocaine exposure did not affect the 5-HT behavioral syndrome elicited by 80H-DPAT. These data indicate that prior cocaine administration does not change 5-HT1A autoreceptor sensitivity (as measured by inhibition of 5-HT synthesis and hyperphagia). However, the attenuated prolactin response to 80H-DPAT suggests that cocaine renders postsynaptic 5-HT1A receptor mechanisms subsensitive in some brain regions. Deficits in 5-HT1A receptor function may underlie feelings of anxiety experienced by cocaine addicts during periods of drug withdrawal.