P.5.041 Differential actions of nicotinic agonists on exploratory behaviour in rats

Abstract

Rats were given unilateral 6-hydroxydopamine lesions and tested 4 weeks later for rotational behavior elicited by either systemic or intranigral injections of dopamine agonists. Subsequently, transplants of fetal (E14) ventral mesencephalic (VM) or cortical tissue were implanted into the lesioned substantia nigra and allowed to develop and integrate within the parenchyma of the host midbrain for a 4-week period before rotational behavior was retested. In animals receiving transplants of fetal VM tissue, systemic injections of amphetamine (5.0 mg/kg, ip) or the D2-agonist, quinpirole (0.2 mg/kg, sc), elicited rotational behavior that was quantitatively similar to rotational behavior observed (1) before animals received transplants of fetal VM tissue or (2) in animals with midbrain transplants of fetal cortical tissue. Intranigral administration of quinpirole (10.0 μg) immobilized most animals and did not elicit rotational behavior in any animals regardless of treatment. Rotational behavior elicited by systemic administration of the D1-agonist, SKF 82958 (0.01 mg/kg, sc), was slightly attenuated by VM transplants placed into the midbrain. Rotational behavior elicited by intranigral injections of SKF 82958 (7.5 μg) was markedly reduced in animals with VM transplants. These data support the hypothesis that midbrain D1-receptors modulate the expression of dopamine agonist-induced rotational behavior.