Buspirone improves 6-hydroxydopamine-induced catalepsy through stimulation of nigral 5-HT(1A) receptors in rats.
Receptors for 5-HT(1A) are widely distributed throughout the basal ganglia, and their activation results in an inhibition of dopamine (DA) release. This study aimed to investigate the effect of buspirone, as a partial agonist of 5-HT(1A) receptors, on 6-hydroxydopamine (6-OHDA)-induced catalepsy in male Wistar rats. Catalepsy was induced by unilateral infusion of 6-OH-DA (6 microg/2 microl/rat) into the central region of the substantia nigra pars compacta (SNc) and assayed by the bar-test method 60, 120 and 180 min after drug administration. The results demonstrated that intraperitoneal (ip) injection of buspirone at doses of 5, 7.5 and 10 mg/kg decreased catalepsy compared with the control group. In addition, intra-SNc injection of 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT; 10 microg/rat), a 5-HT(1A) receptor agonist, decreased 6-OHDA-induced catalepsy. The effects of buspirone (7.5 mg/kg, ip) and 8-OH-DPAT (10 microg/rat, intra-SNc) were abolished by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl]piperazine hydrobromide (NAN-190; 10 microg/rat, intra-SNc), a 5-HT(1A) receptor antagonist. Our study indicates that buspirone improves catalepsy in a 6-OHDA-induced animal model of Parkinson's disease through activation of nigral 5-HT(1A) receptors. However, further investigations should be undertaken to clarify the exact mechanism of interaction between 5-HT(1A) and DA receptors.
Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664, Iran. nayebia@yahoo.com
Alireza M
AM
Nayebi
Siyamak R
SR
Rad
Mehdi
M
Saberian
Saeid
S
Azimzadeh
Morteza
M
Samini
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000627:therapeutic use; D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D016627:Oxidopamine; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D002065:Buspirone