Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition - PubMed (original) (raw)

Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition

L Ugedo et al. Psychopharmacology (Berl). 1989.

Abstract

The effect of systemic administration of ritanserin (R 55667), a 5-hydroxytryptamine (5-HT2) receptor antagonist, on midbrain dopamine (DA) neurons was studied with single cell recording techniques in the chloral hydrate anesthetized male rat. Dopamine cells of the zona compacta, substantia nigra (ZC-SN) and the ventral tegmental area (VTA) were identified by established criteria. Ritanserin (0.5-2.0 mg/kg, IV) dose-dependently increased both the burst firing and firing rate of the midbrain DA neurons. These effects were prevented by endogenous 5-HT depletion through pretreatment with the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA, 300 mg/kg, IP, x3), which did not significantly alter the firing characteristics of the midbrain DA cells when given alone. These results suggest that 5-HT exerts an inhibitory control of midbrain DA cell activity mediated by 5-HT2 receptors. The stimulatory effect of ritanserin on midbrain DA systems might contribute to some of its clinical effects, such as improvement of mood, drive and motivation as well as its therapeutic actions in parkinsonism and type II schizophrenia.

PubMed Disclaimer

References

    1. Science. 1983 May 27;220(4600):974-7 - PubMed
    1. Brain Res. 1987 Oct 13;423(1-2):347-52 - PubMed
    1. Exp Brain Res. 1988;69(2):444-8 - PubMed
    1. Mol Pharmacol. 1985 Jun;27(6):600-11 - PubMed
    1. Eur J Pharmacol. 1983 Jul 22;91(2-3):189-96 - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources