Increased dopamine receptor sensitivity in the rat following acute administration of sufentanil, U50,488H and D-Ala2-D-Leu5-enkephalin.
The effects of acutely administered opioid receptor agonists sufentanil, U50,488H and [D-Ala2,D-Leu5]-enkephalin (DADL) were observed upon dopamine D1 and D2 binding site density in the striatum of the rat. In addition, the functional implications of opioid-induced changes in dopamine receptor sensitivity were studied using the behavioural profile elicited by apomorphine in the rat. The mu-agonist sufentanil (1 or 20 micrograms/kg, i.p.), the kappa-agonist U50,488H (10 mg/kg, i.p.) and DADL (1 microgram/animal, i.c.v.) all significantly elevated D2 but not D1 binding site density in rat striatum. Pretreatment with sufentanil (1 microgram/kg, i.p.) induced an elevation in apomorphine-induced stereotyped behaviour, but attenuated locomotor activity. Following administration of U50,488H (10 mg/kg, i.p.), both the degree of stereotypy and the intensity of the locomotor activity were enhanced. Contralateral rotation was observed in animals pretreated with DADL (1 microgram/animal, i.c.v.) following challenge with apomorphine. It is concluded that the opioid agonists studied induce a significant elevation in functional D2 sites to the exclusion of D1 sites. However, the precise mechanism by which this effect is elicited remains to be established.[1]References
- Increased dopamine receptor sensitivity in the rat following acute administration of sufentanil, U50,488H and D-Ala2-D-Leu5-enkephalin. Rooney, K.F., Armstrong, R.A., Sewell, R.D. Naunyn Schmiedebergs Arch. Pharmacol. (1991) [Pubmed]
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