Central 5-HT4 receptors and dopamine-dependent motor behaviors: Searching for a functional role
Pharmacology Biochemistry and Behavior. 2002-04-01; 71(4): 627-633
DOI: 10.1016/S0091-3057(01)00703-1
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De Deurwaerdère P(1), Cervo L, Stinus L, Spampinato U.
Author information:
(1)Laboratoire Neuropsychobiologie des Désadaptations, UMR-CNRS 5541, Université
Victor Segalen Bordeaux 2, B.P. 31, 146 rue Léo-Saignat, 33077 Cedex, Bordeaux,
France.
In this study, we evaluated the role of central 5-HT(4) receptors in the control
of motor behaviors related to change of nigrostriatal dopamine (DA)
transmission, namely, stereotyped behavior and catalepsy in rats. Indeed, given
that 5-HT(4) receptors indirectly modulate nigrostriatal DA neuron activity, we
hypothesized that these receptors would regulate nigrostriatal DA transmission
in the basal ganglia, and consequently, associated motor responses. Stereotypy
was induced either by an acute administration of apomorphine (0.3 and 1.5 mg/kg
sc), or by a single morphine administration (15 mg/kg sc) in chronically
morphine-treated (15 mg/kg sc, twice daily for 10 days) rats. Catalepsy was
induced by the typical neuroleptic haloperidol (HAL; 1 mg/kg sc). The selective
5-HT(4) antagonist, GR 125487 (1 mg/kg ip), modified neither apomorphine- nor
morphine-induced stereotypy. HAL-induced catalepsy, while reduced by the
systemic administration of the 5-HT(1A) agonist 8-OH-DPAT (0.1 mg/kg sc), was
insensitive to GR 125487, systemically (1, 3, 10 mg/kg ip) or locally (20 and 40
nmol/20 microl) administered into the third ventricle. Also, HAL-induced
catalepsy was not affected by the selective 5-HT(4) antagonist GR 113808 (3
mg/kg ip). The obtained results indicate that 5-HT(4) receptor antagonism does
not modulate motor behaviors related to change of striatal DA transmission.