DTG-induced circling behaviour in rats may involve the interaction between sigma sites and nigro-striatal dopaminergic pathways.
The distribution of sigma sites in brain areas enriched in dopamine, and the finding that circling behaviour can be elicited by specific sigma ligands such as DTG (di-o-tolylguanidine) suggest a modulatory role of these sites in the dopaminergic system. The present study was carried out to investigate further this hypothesis. Circling behaviour induced in rats by unilateral intranigral injection of DTG (10 nmol/rat) was decreased by haloperidol (0.1 mg/kg, i.p.), clebopride (0.25 mg/kg, i.p.) and SCH 23390 (0.03 mg/kg, s.c.) indicating that an interaction between sigma sites and the midbrain dopaminergic system may be involved in this rotational behaviour. Microdialysis experiments in freely moving rats showed that unilateral intranigral injection of DTG (5, 10, 20 nmol/rat) produced increases in extracellular levels of dopamine metabolites (DOPAC, HVA) in the ipsilateral striatum which correlated with the number of rotations. In addition intranigral injection of DTG (10 nmol/rat) produced increases in tissular dopamine metabolite levels in the ipsilateral striatum without affecting dopamine metabolite levels in limbic structures. These results indicate that sigma sites may be involved in the modulation of the dopaminergic motor system.
Bastianetto
S
S
Synthelabo Recherche, Bagneux, France.
Rouquier
L
L
Perrault
G
G
Sanger
D J
DJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006146:Guanidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D000927:Anticonvulsants; D065127:Dopamine D2 Receptor Antagonists; D006146:Guanidines; D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D015102:3,4-Dihydroxyphenylacetic Acid; C050232:1,3-ditolylguanidine; D004298:Dopamine; D006719:Homovanillic Acid