Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists in the rat.
U Liminga, A E Johnson, P E Andrén, L M Gunne
Pharmacology, biochemistry, and behavior October 1993 DOI: 10.1016/0091-3057(93)90375-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Awake rats |
| Interventions | (R)-8-hydroxy-2-(di-propylamino)-tetralin (8-OH-DPAT) (-)-(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301) 5-methoxy-N N-dimethyltryptamine hydrogen oxalate (5-MeO-DMT) 1-(3-triflouro-methylphenyl) piperazine (TFMPP) 1(m-chlorophenyl)-piperazine (mCPP) 2-methyl-5-hydroxytryptamine (2-Me-5-HT) 1-phenylbiguanide 1-(4-bromophenyl-2 5-dimethoxy)-2-aminopropane (DOB) |
| Dose | 1.3-13 nmol on each side (8-OH-DPAT); 5- to 10-nmol doses (TFMPP, mCPP, 2-Me-5-HT) |
| Key findings | Intranigral infusion of 5-HT1A agonists (8-OH-DPAT, 5-MeO-DMT) dose-dependently reduced vacuous chewing movements in rats, an effect blocked by a 5-HT1A antagonist, whereas nonspecific 5-HT agonists (TFMPP, mCPP) and a 5-HT3 agonist (2-Me-5-HT) increased chewing at 5-10 nmol doses. The authors suggest the increased chewing was mediated via nigral 5-HT1B receptors and discuss the importance of serotonergic mechanisms in drug-induced dyskinesias. |
Abstract
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-HT1A 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-HT1A antagonist [(-)-(S)-5-fluoro-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 frequencies. Intranigral infusion of the nonspecific 5-HT-agonists 1-(3-triflouro-methylphenyl) piperazine (TFMPP) and 1(m-chlorophenyl)-piperazine (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 most 5-HT receptors in the SNr are of the 5-HT1B subtype, these results suggest that the increased VCM frequency was mediated via nigral 5-HT1B receptors. The importance of 5-HTergic mechanisms in the development of drug-induced dyskinesias is discussed.