Effects of 5-HT, 5-HT and 5-HT receptor agonists and antagonists on responding for a conditioned reinforcer and its enhancement by methylphenidate.

OBJECTIVES

These experiments examined the effects of selective 5-HT, 5-HT and 5-HT receptor ligands on responding for a conditioned reinforcer (CRf). Effects of these ligands were measured under basal conditions and following elevated dopamine (DA) activity produced by the DA reuptake inhibitor methylphenidate.

METHODS

Water-restricted rats learned to associate a conditioned stimulus (CS) with water in operant chambers. Subsequently, two response levers were made available; responding on one lever delivered the CS (now a CRf), while responding on the second lever had no consequences. The effects of agonist and antagonists of 5-HT (8-hydroxy-2(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635)), 5-HT (DOI and M100907) and 5-HT (Ro60-0175 and SB242084) receptors on responding were examined alone, as well as in the presence of methylphenidate.

RESULTS

Responding for a CRf was reduced by the agonists 8-OH-DPAT, DOI and Ro60-0175. 8-OH-DPAT also reduced responding for water and seemed to impair responding in a non-specific fashion. None of the receptor antagonists affected responding. Methylphenidate dose-dependently enhanced responding for a CRf, and this was attenuated by DOI and Ro60-0175. Conversely, the 5-HT receptor antagonist SB242084 potentiated the effect of methylphenidate.

CONCLUSIONS

No evidence was found for a behaviourally selective effect of 5-HT receptor ligands on responding for a CRf. Activation of 5-HT receptors selectively inhibits responding for a CRf. 5-HT receptor ligands exerted bidirectional modulation of responding for a CRf, especially when DA activity was increased. This indicates that 5-HT receptor activity is an important modulator of DA-dependent reward-related behaviours.