Opioid receptors and inhibition of dopamine-sensitive adenylate cyclase in slices of rat brain regions receiving a dense dopaminergic input

Abstract

Listen

Translate article

In slices of rat nucleus accumbens, olfactory tubercle, frontal cortex and mediobasal hypothalamus exposed to dopamine (DA), the activation of DA D 1 receptors stimulated cyclic AMP (cAMP) formation whereas, in nucleus accumbens slices only, activation of D 2 receptors appeared to inhibit D 1 receptor-stimulated adenylate cyclase at the same time. Activation of μ-opioid receptors by [D-Ala 2,MePhe 4,Gly-ol 5]enkephalin (DAMGO; 1 μM),but not of δ-opioid receptors by 1 μM [D-Pen 2,D-Pen 5]enkephalin (DPDPE), inhibited (by 35–40%) DA-stimulated cAMP production in slices of nucleus accumbens and olfactory tubercle. When adenylate cyclase was stimulated by selective D 1 receptor activation, i.e. by DA in the presence of (−)-sulpiride, DPDPE reduced cAMP formation (by about 45%) in nucleus accumbens slices but not in slices of the other brain dregions. The κ-agonist, U 50,488, did not affect DA- or D 1 receptor-stimulated adenylate cyclase activity in any of the brain regions. Preincubation of nucleus accumbens slices with the irreversible δ-ligand, fentanyl isothiocyanate (FIT; 1 μM), not only antagonized the inhibitory effect of DPDPE but also prevented the antagonism by naloxone of the inhibitory effect of DAMGO. Therefore in nucleus accumbens opioids may inhibit DA-sensitive adenylate cyclase through activation of a μ/δ-opioid receptor complex, whereas in olfactory tubercle μ-receptors appear to mediate the inhibition of adenylate cyclase activity. Opioids do not seem to affect DA-stimulated cAMP formation in frontal cortex and mediobasal hypothalamus.