Involvement of 5-HT3 receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviours in the rat

1 The present study investigated the central effects of the selective serot onin reuptake inhibitor (SSRI) fluoxetine and the role of 5-hydroxytryptami ne(3) (5-HT3) receptors in the core of the nucleus accumbens (NAc) on cocai ne-induced behavioural changes in rats. 2 The 5-HT3 receptor antagonist ondansetron (1 or 10 ng) was microinjected bilaterally into the core of the NAc 60 min prior to peripheral cocaine (15 mg kg(-1), i.p.) administration followed by the assessment of locomotor ac tivity, rearing activity and head bobs. Both doses of ondansetron attenuate d cocaine's stimulatory effect on behaviours. 3 Fluoxetine (0.05 or 5 mug) microinjected bilaterally into the core of the NAc 30 min before peripheral administration of cocaine produced dose-depen dent biphasic effects on cocaine-induced behaviours. Intra-NAc administrati on of 0.05 mug fluoxetine resulted in a potentiation of cocaine-induced beh aviours, while the higher dose of the SSRI (5 mug) attenuated the stimulant effect of cocaine on behaviours. 4 To investigate a possible involvement of 5-HT3 receptors in fluoxetine's facilitatory action, ondansetron (10 ng) was microinjected 30 min prior to fluoxetine (0.05 mug), which resulted in a significant attenuation of the f acilitatory effect of fluoxetine on cocaine-induced behaviours. 5 Thus, 5-HT3 receptors in the core of the NAc appear to mediate stimulator y effects on cocaine induced locomotor activity, rears and head bobs, where as the attenuation of cocaine-induced behaviours by fluoxetine at the highe r dose. suggests the involvement of a different 5-HT receptor subtype.