TY - JOUR
T1 - Central 5-HT4 receptors and dopamine-dependent motor behaviors
T2 - Searching for a functional role
AU - De Deurwaerdère, Philippe
AU - Cervo, Luigi
AU - Stinus, Luis
AU - Spampinato, Umberto
PY - 2002
Y1 - 2002
N2 - In this study, we evaluated the role of central 5-HT4 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-HT4 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-HT4 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-HT1A 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 μl) administered into the third ventricle. Also, HAL-induced catalepsy was not affected by the selective 5-HT4 antagonist GR 113808 (3 mg/kg ip). The obtained results indicate that 5-HT4 receptor antagonism does not modulate motor behaviors related to change of striatal DA transmission.
AB - In this study, we evaluated the role of central 5-HT4 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-HT4 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-HT4 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-HT1A 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 μl) administered into the third ventricle. Also, HAL-induced catalepsy was not affected by the selective 5-HT4 antagonist GR 113808 (3 mg/kg ip). The obtained results indicate that 5-HT4 receptor antagonism does not modulate motor behaviors related to change of striatal DA transmission.
KW - 5-HT receptors
KW - Apomorphine
KW - Catalepsy
KW - GR 113808
KW - GR 125487
KW - Haloperidol
KW - Morphine
KW - Stereotypy
UR - http://www.scopus.com/inward/record.url?scp=0036122521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036122521&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(01)00703-1
DO - 10.1016/S0091-3057(01)00703-1
M3 - Article
C2 - 11888554
AN - SCOPUS:0036122521
VL - 71
SP - 627
EP - 633
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 4
ER -