Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists in the rat

Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the substantia nigra pars reticulata (SNr) of awake rats was shown to influence oral behavior. The 5-HT 1A agonist ( R)-8-hydroxy-2-(di-propylamino)-tetralin (8-OH-DPAT) (1.3–13 nmol on each side) produced a dose-dependent depression of vacuous chewing movements (VCMs) that lasted about 20 min. The ( R)-8-OH-DPAT-induced depression of VCMs was blocked by the simultaneous intranigral infusion of a specific 5-HT 1A antagonist [(−)-( S)-5-flouro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301)], which had no effect when given alone. Another 5-HT 1A agonist [(5-methoxy- N, N-dimethyltryptamine hydrogen oxelate (5-MeO-DMT) also reduced VCM frequencies. Intranigral infusion of the nonspecific 5-HT-agonist 1-(3-triflouro-methylphenyl) piperazine (TFMPP) and 1( m-chlorophenyl-piperazine (mCPP) and a 5-HT 3 agonist [2-methyl-5-hydroxytrytapamine (2-Me-5-HT)] increased VCM after 5- to 10-nmol doses. Another 5-HT 3 agonist (1-phenylbiguanide) and a 5-HT 2 agonist [1-(4-bromophenyl-2,5-dimethoxy)-2-aminopropane (DOB)] had no significant effect. As most 5-HT receptors in the SNr are of the 5-HT 1B subtype, these results suggest that the increased VCM frequency was mediated via nigral 5-HT 1B receptors. The importance of 5-HTergic mechanisms in the development of drug-induced dyskinesias is discussed.