Pharmacological evidence for the involvement of sigma sites in DTG-induced contralateral circling in rats.
The central distribution of sigma sites labelled by di-o-tolylguanidine (DTG), a compound which has specific affinity for sigma sites, and its ability to produce postural movements, are consistent with the hypothesis that sigma sites may play a functional role in the regulation of movement. The aim of the present study was to evaluate the specificity of the circling behaviour induced by unilateral intranigral injection of DTG in rats. As previously described, DTG produced dose-dependent unilateral rotations (2.5-20 nmol/rat). A similar dose-dependent circling behaviour was observed with DMTG and (+) NANM (3-40 nmol/rat), compounds which bind to both sigma and PCP sites, and with haloperidol (3-20 nmol/rat) whereas raclopride and D,L-sulpiride did not elicit any circling (10 nmol/rat). DTG-induced circling after intranigral injection (10 nmol/rat) was decreased in a dose-dependent manner by rimcazole (20-40 mg/kg, i.p.), a selective ligand for sigma sites, and by BMY 14802 (3, 10, 30 mg/kg, i.p.), ifenprodil and eliprodil (1, 3, 10 mg/kg, i.p.), non-selective sigma ligands. In contrast, naloxone (1 mg/kg, s.c.) and CGS 19755 (1, 3, 10 mg/kg, i.p.) did not change the DTG-induced circling. Eliprodil failed to inhibit circling produced by compounds devoid of any affinity for sigma sites such as APV, dizocilpine or muscimol, indicating the specificity of the inhibition observed with eliprodil on the DTG-induced circling.(ABSTRACT TRUNCATED AT 250 WORDS)
Bastianetto
S
S
Synthelabo Recherche, Bagneux, France.
Perrault
G
G
Sanger
D J
DJ
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002227:Carbazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology
D000927:Anticonvulsants; D002227:Carbazoles; D006146:Guanidines; D017480:Receptors, sigma; D012457:Salicylamides; D020891:Raclopride; C012134:SK&F 10047; C034931:rimcazole; D010620:Phenazocine; D006220:Haloperidol; C050232:1,3-ditolylguanidine