Central 5-HT(4) receptors and dopamine-dependent motor behaviors: searching for a functional role.
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.
De Deurwaerdère
Philippe
P
Laboratoire Neuropsychobiologie des Désadaptations, UMR-CNRS 5541, Université Victor Segalen Bordeaux 2, B.P. 31, 146 rue Léo-Saignat, 33077 Cedex, Bordeaux, France.
Cervo
Luigi
L
Stinus
Luis
L
Spampinato
Umberto
U
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D002490:Central Nervous System / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000502:physiology*; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007211:Indoles; D009294:Narcotics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D044422:Receptors, Serotonin, 5-HT4; D009020:Morphine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006220:Haloperidol; D001058:Apomorphine; D004298:Dopamine; C082871:GR 113808