DOI, A 5-HT2A 2C RECEPTOR AGONIST, POTENTIATES AMPHETAMINE-INDUCED DOPAMINE RELEASE IN RAT STRIATUM/

The effects of(+/-)-DOI (1-(2,5-dimethoxy-4-iodophenyl)-aminopropane) hydrochloride, a mixed 5-HT2A/2C receptor agonist, on the release of d opamine (DA) following D-amphetamine sulfate (AMP) or a DA D-2 autorec eptor selective dose of (-)-apomorphine hydrochloride (APO), were inve stigated in rat striatum (STR) and nucleus accumbens (NAG), using in v ivo microdialysis. AMP (1.0 mg/kg, s.c.) produced marked increases in extracellular DA levels in both the STR and the NAC whereas DOI (2.5 m g/kg, i.p.) alone had no significant effect on extracellular DA levels in either region. Pretreatment with DOI 30 min prior to AMP, further enhanced the AMP-induced increase in striatal extracellular DA levels. On the other hand, DOI pretreatment attenuated the APO (50 mu g/kg, s .c.)-induced decrease in extracellular DA levels in the STR. Pretreatm ent with DOI did not affect the ability of either AMP or APO to modula te extracellular DA levels in the NAC. These results provide further e vidence that 5-HT2A/2C receptors modulate the release mechanisms of DA in the STR. Possible mechanisms are discussed.