Autoradiographic localization of delta opioid receptors within the mesocorticolimbic dopamine system using radioiodinated [2-D-penicillamine, 5-D-penicillamine]enkephalin (125I-DPDPE).
The enkephalin analog [2-D-penicillamine, 5-D-penicillamine]enkephalin was radioiodinated (125I-DPDPE) and shown to retain a pharmacological selectivity characteristic of the delta opioid receptor in in vitro binding studies. The distributions of 125I-DPDPE binding, using in vitro autoradiographic techniques, were similar to those previously reported for the delta opioid receptor. The nucleus accumbens, striatum, and medial prefrontal cortex contain dense gradients of 125I-DPDPE binding in regions known to receive dopaminergic afferents emanating from the mesencephalic tegmentum. Selective chemical lesions of the ventral tegmental area and substantia nigra were employed to deduce the location of the 125I-DPDPE binding within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area and substantia nigra produced by mesencephalic injection of 6-hydroxydopamine resulted in significant (20-30%) increases in 125I-DPDPE binding contralateral to the lesion within the striatum and nucleus accumbens. Lesions of the perikarya (dopaminergic and nondopaminergic) of the ventral tegmental area, induced by quinolinic acid injections, caused increases of less magnitude within these same nuclei. No significant alterations in 125I-DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confirmed by immunocytochemistry for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists acting through delta opioid receptors do not directly modulate dopaminergic afferents but do regulate postsynaptic targets of the mesocorticolimbic dopamine system.
Dilts
R P
RP
Department of Veterinary Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520.
Kalivas
P W
PW
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins; D006892:Hydroxydopamines; D007120:Immunochemistry; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008032:Limbic System / Q000378:metabolism*; D008297:Male; D016627:Oxidopamine; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013563:Sympathectomy, Chemical; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology
D004745:Enkephalins; D006892:Hydroxydopamines; D007457:Iodine Radioisotopes; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D011813:Quinuclidinyl Benzilate; D020881:Enkephalin, D-Penicillamine (2,5)-; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase