The enkephalin analog (2‐D‐Penicillamine, 5‐D‐Penicillamine)enkephalin was radioiodinated 125I‐DPDPE and shown to retain a pharmacological selectivity characteristic 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 within particular regions of the mesocorticolimbic dopamine system. Unilateral lesions of dopamine perikarya (A9 and A10) within the ventral tegmental area nd substantia nigra produced by mesencephalic injection of 6‐hydroxydopamine resulted in significant (20–30%) increase 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 aquinolinic and injections, caused increases of less magnitude within these same nuclei. No significant alteratons in 125I‐DPDPE binding were observed within the mesencephalon as a result of either treatment. The specificity of the lesions was confiremed by immunocytochemistry for tyrosine for tyrosine hydroxylase. These results suggest that the enkephalins and opioid agonists through delta opioid receptors do not dircetly modulate dopaminergic afferents but do regulate postsnaptic targets of the mesocorticolimbic dopamine system.
Synapse – Wiley
Published: Jan 1, 1990
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