Inhibition of guinea pig lordosis behavior by the phenylethanolamine N-methyltransferase (PNMT) inhibitor SKF-64139: mediation by alpha noradrenergic receptors

Experiments were undertaken to determine whether the steroid-dependent lordosis response of female guinea pigs is under adrenergic control. In initial experiments, treatment with the centrally active phenylethanolomine N-methyltransferase (PNMT; the enzyme catalyzing methylation of norepinephrine to epinephrine) inhibitor SKF-64139 inhibited lordosis behavior induced by estradiol-17 beta benzoate plus progesterone. SKF-29661, a PNMT inhibitor that does not cross the blood-brain barrier, did not affect lordosis. However, no detectable epinephrine was found in brain or spinal cord of drug- or vehicle-treated guinea pigs. This suggests that epinephrine neuronal systems do not exist in the guinea pig CNS. In agreement with this idea, the inhibitory effects of SKF-64139 on lordosis were found to be primarily attributable to the blockade of alpha noradrenergic receptors rather than to PNMT inhibition. Two lines of evidence support this conclusion. First, using in vitro receptor binding techniques, SKF-64139 was found to have a relatively high affinity for alpha 1 and particularly alpha 2 receptors in guinea pig forebrain. Second, presumably through competitive inhibition of SKF-64139 binding to alpha receptors, treatment with clonidine (an alpha receptor agonist) overrode the inhibitory effects of SKF-64139 on lordosis. Taken together, these findings indicate the possible absence of epinephrine neuronal systems in guinea pig brain and reemphasize the importance of alpha receptors in regulating steroid-dependent lordosis behavior in this species.