Ultrastructural evidence for enkephalin mediated disinhibition in the ventromedial nucleus of the hypothalamus.

The ventromedial nucleus of the hypothalamus (VMN) regulates the estrogen-dependent appearance of female mating behavior, lordosis. Accumulating evidence suggests that estrogen might exert its control over lordosis by acting, in part, on neurons that contain enkephalin in the VMN. The expression of the enkephalin precursor gene is robustly stimulated by estrogen and is correlated with the later appearance of lordosis. GABA has also been implicated as an important neurotransmitter for the appearance of lordosis. Because enkephalin is thought to act in several brain areas to modulate the activity of GABAergic neurons, we studied the ultrastructural morphology and relationship between neurons containing these neurochemicals using dual-labeling immunocytochemistry in ovariectornized rats, half of which received estrogen replacement. Immunolabeling for enkephalin was almost always detected within axon terminals (695 axonal profiles sampled), while GABA immunoreactivity was more often localized to cell bodies and dendrites (191 profiles), than to axons (63 profiles). Axon terminals containing enkephalin immunolabeling provided a major innervation to soma or dendrites containing GABA. That is, over one third (94/245) of the axon terminals in contact with GABA-immunoreactive dendrites contained enkephalin. Furthermore, these GABA-immunoreactive dendrites accounted for a fifth of the somatodendritic processes associated with enkephalin-containing axon terminals. These findings support the hypothesis that enkephalin may act in the VMN by inhibiting GABAergic neurons, which could result in the disinhibition of neural circuits relevant for lordosis.