Involvement of 5‐HT 3 receptors in the nucleus accumbens in the potentiation of cocaine‐induced behaviours in the rat

The present study investigated the central effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the role of 5‐hydroxytryptamine 3 (5‐HT 3 ) receptors in the core of the nucleus accumbens (NAc) on cocaine‐induced behavioural changes in rats. The 5‐HT 3 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 activity, rearing activity and head bobs. Both doses of ondansetron attenuated cocaine's stimulatory effect on behaviours. Fluoxetine (0.05 or 5 μg) microinjected bilaterally into the core of the NAc 30 min before peripheral administration of cocaine produced dose‐dependent biphasic effects on cocaine‐induced behaviours. Intra‐NAc administration of 0.05 μg fluoxetine resulted in a potentiation of cocaine‐induced behaviours, while the higher dose of the SSRI (5 μg) attenuated the stimulant effect of cocaine on behaviours. To investigate a possible involvement of 5‐HT 3 receptors in fluoxetine's facilitatory action, ondansetron (10 ng) was microinjected 30 min prior to fluoxetine (0.05 μg), which resulted in a significant attenuation of the facilitatory effect of fluoxetine on cocaine‐induced behaviours. Thus, 5‐HT 3 receptors in the core of the NAc appear to mediate stimulatory effects on cocaine‐induced locomotor activity, rears and head bobs, whereas the attenuation of cocaine‐induced behaviours by fluoxetine at the higher dose, suggests the involvement of a different 5‐HT receptor subtype.British Journal of Pharmacology (2000) 131 , 1294–1302; doi: 10.1038/sj.bjp.0703687