MODULATION OF ORAL MOVEMENTS BY INTRANIGRAL 5-HYDROXYTRYPTAMINE RECEPTOR AGONISTS IN THE RAT

Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the sub stantia nigra pars reticulata (SNr) of awake rats was shown to influen ce oral behavior. The 5-HT1A agonist (R)-8-hydroxy-2-(di-propylamino)- tetralin (8-OH-DPAT) (1.3-13 nmol on each side) produced a dose-depend ent depression of vacuous chewing movements (VCMs) that lasted about 2 0 min. The (R)-8-OH-DPAT-induced depression of VCMs was blocked by the simultaneous intranigral infusion of a specific 5-HT1A, antagonist )- (S)-5-flouro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301)], which had no effect when given alone. Another 5-HT1A agonist [(5-methoxy-N,N -dimethyltryptamine hydrogen oxalate (5-MeO-DMT)] also reduced VCM fre quencies. Intranigral infusion of the nonspecific 5-HT-agonists 1-(3-t riflouro-methylphenyl) piperazine (TFMPP) and 1(m-chlorophenyl)-pipera zine (mCPP) and a 5-HT3 agonist [2-methyl-5-hydroxytryptamine (2-Me-5- HT)] increased VCM after 5- to 10-nmol doses. Another 5-HT3 agonist (1 -phenylbiguanide) and a 5-HT2 agonist [1-(4-bromophenyl-2, 5-dimethoxy )-2-aminopropane (DOB)] had no significant effect. As mast 5-HT recept ors in the SNr are of the 5-HT1B subtype, these results suggest that t he increased VCM frequency was mediated via nigral 5-HT1B receptors. T he importance of 5-HTergic mechanisms in the development of drug-induc ed dyskinesias is discussed.