Involvement of 5-HT(3) receptors in the nucleus accumbens in the potentiation of cocaine-induced behaviours in the rat

Abstract

1. 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. 2. 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. 3. Fluoxetine (0.05 or 5 microg) 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 microg fluoxetine resulted in a potentiation of cocaine-induced behaviours, while the higher dose of the SSRI (5 microg) attenuated the stimulant effect of cocaine on behaviours. 4. 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 microg), which resulted in a significant attenuation of the facilitatory effect of fluoxetine on cocaine-induced behaviours. 5. 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.

Figure 1

(a) Locomotor activity, (b) rears and (c) head bobs induced by 15 mg kg⁻¹ cocaine (C) or saline (S) injected i.p. at time 0 in rats pretreated by intra-NAc administration of saline (S) 30 min earlier and ondansetron (O) 1 or 10 ng or saline (S) 60 min earlier. The values represent mean scores+s.e.mean (number of rats used for each treatment group are shown in parentheses). ^*P<0.05 (Student–Newman–Keuls test), O 1 ng-S-C and O 10 ng-S-C compared to S-S-C.

Figure 2

(a) Locomotor activity, (b) rears and (c) head bobs induced by 15 mg kg⁻¹ cocaine (C) or saline (S) injected i.p. at time 0 in rats pretreated by intra-NAc administration of fluoxetine (F) 0.05 or 5 μg or saline (S) 30 min earlier and saline (S) 60 min earlier. The values represent mean scores+s.e.mean (number of rats used for each treatment are shown in parentheses). ^*P<0.05 (Student–Newman–Keuls test, Dunn's test), S-F 5 μg-S compared to S-S-S and S-F 0.05 μg-C and S-F 5 μg-C compared to S-S-C.

Figure 3

(a) Locomotor activity, (b) rears and (c) head bobs induced by 15 mg kg⁻¹ cocaine (C) or saline (S) injected i.p. at time 0 in rats pretreated by intra-NAc administration of fluoxetine (F) 0.05 μg or saline (S) 30 min earlier and ondansetron (O) 10 ng or saline (S) 60 min earlier. The values represent mean scores+s.e.mean (number of rats used for each treatment are shown in parentheses). ^*P<0.05 (Student–Newman–Keuls test), O 10 ng-F 0.05 μg-C compared to S-F 0.05 μg-C.