The role of neuroplasticity in cholinergic neurons of the laterodorsal tegmental nucleus for cocaine addiction.

Abstract

A large body of literature indicates that neural adaptations induced by cocaine in the mesocorticolibic system cause addictive behaviors. Emerging evidence suggests that the laterdorsal tegmental nucleus (LDT), which contains cholinergic, glutamatergic and GABAergic neurons and innervates the ventral tegmental area (VTA), might also contribute to the development of cocaine addiction. In this review, we summarize our recent findings showing that neuroplasticity elicited by cocaine administration in LDT cholinergic neurons is involved in the expression of addictive behaviors. Ex vivo electrophysiological recordings obtained from repeatedly cocaine administered rats revealed and increased excitatory synaptic transmission to and enhanced intrinsic membrane excitability in LDT cholinergic neurons. The former depended on enhanced glutamate release probability form presynaptic terminals and the latter was mediated by increased persistent sodium conductance. Additionally, intra-LDT administration of AMPA/HMDA receptor antagonists or a persistent sodium channel blocker attenuated the expression of cocaine-induced conditioned place preference. These findings suggest that chronic cocaine exposure-induced neuroplasticity in LDT cholinergic neurons may activate LDT cholinergic neurons, which in turn may enhance the activity of dopamine neurons in the VTA, leading to the development of cocaine addiction.