Cholinergic antagonists in ventral tegmentum elevate thresholds for lateral hypothalamic and brainstem self-stimulation.

Frequency thresholds for lateral hypothalamic self-stimulation are elevated following microinjections of atropine into ventral tegmentum (73). Many self-stimulation sites in brainstem are situated near cholinergic cell groups and axons, and ventral tegmentum receives cholinergic afferents terminals. To test the hypothesis that ventral tegmental muscarinic receptors are involved in lateral hypothalamic and brainstem self-stimulation, stimulating electrodes were placed in lateral hypothalamus and dorsal tegmentum near the midbrain-pons border, and cannulae were implanted in ventral tegmentum. Microgram injections of muscarinic antagonists, atropine or scopolamine, or a choline uptake blocker, hemicholinium-3, elevated frequency thresholds for both self-stimulation sites in a dose-dependent and time-dependent fashion. In addition, summation and collision between the two self-stimulation sites was tested using paired-pulse methods (53). Summation ranged from 31 to 87% (i.e., 24 to 47% reductions in frequency threshold were observed at long intrapair intervals), but no collision-like effects were observed at short intrapair intervals. The ventral tegmentum is a likely site for the convergence of dorsal tegmental and lateral hypothalamic self-stimulation pathways.