A SUBSET OF VENTRAL TEGMENTAL AREA NEURONS IS INHIBITED BY DOPAMINE, 5-HYDROXYTRYPTAMINE AND OPIOIDS

Neurons originating in the ventral tegmental area are thought to play a key role in the formation of addictive behaviors, particularly in re sponse to drugs such as cocaine and opioids. In this study we identifi ed different populations of ventral tegmental area neurons by the phar macology of their evoked synaptic potentials and their response to dop amine, 5-hydroxytryptamine and opioids. Intracellular recordings were made from ventral tegmental area neurons in horizontal slices of guine a-pig brain and electrical stimulation was used to evoke synaptic pote ntials. The majority of cells (61.3%) hyperpolarized in response to do pamine, depolarized to 5-hydroxytryptamine, failed to respond to [Met] (5)enkephalin and exhibited a slow GABA(B)-mediated inhibitory postsyn aptic potential. A smaller proportion of cells (11.3%) hyperpolarized in response to [Met](5)enkephalin, depolarized to 5-hydroxytryptamine, failed to respond to dopamine and did not exhibit a slow inhibitory p ostsynaptic potential. These two groups of cells corresponded to previ ously described ''principal'' and ''secondary'' cells, respectively. A further group of cells (27.4%) was identified that, like the principa l cells, hyperpolarized to dopamine. However, these ''tertiary cells'' also hyperpolarized to both 5-hydroxytryptamine and [Met](5)enkephali n and exhibited a slow, cocaine-sensitive 5-hydroxytryptamine(1A)-medi ated inhibitory postsynaptic potential. When principal and tertiary ce lls were investigated immunohistochemically, 82% of the principal cell s were positive for tyrosine hydroxylase compared with only 29% of the tertiary cells. The 5-hydroxytryptamine innervation of both these cel l types was investigated and a similar density of putative contacts wa s observed near the somata and dendrites in both groups. This latter f inding suggests that the existence of a 5-hydroxytryptamine-mediated i nhibitory postsynaptic potential in the tertiary cells may be determin ed by the selective expression of 5-hydroxytryptamine receptors, rathe r than the distribution or density of the 5-hydroxytryptamine innervat ion. We conclude that tertiary cells are a distinct subset of ventral tegmental area neurons where cocaine and mu-opioids both mediate inhib ition. Copyright (C) 1997 IBRO.