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.
Rooney
K F
KF
Division of Pharmacology, Welsh School of Pharmacy, University of Wales College of Cardiff, United Kingdom.
Armstrong
R A
RA
Sewell
R D
RD
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D017409:Sufentanil; D014316:Tritium
D001552:Benzazepines; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D014316:Tritium; D013134:Spiperone; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D017409:Sufentanil; D005283:Fentanyl