The contribution of neuroplasticity induced in cholinergic neurons of the laterodorsal tegmental nucleus to cocaine addiction.

Cocaine-induced neuroplasticity in brain reward circuitry consisting of the ventral tegmental area (VTA), nucleus accumbens and medial pre- frontal cortex is critical for developing cocaine addiction. Recent studies have investigated the involvement of brain areas in addition to the mesocorticolimbic circuitry in cocaine addiction. One such area is the laterodorsal tegmental nucleus (LDT). Cholinergic neurons in the LDT project to the VTA and regulate the activity of dopaminergic neurons. Using the cocaine-induced conditioned place preference (CPP) paradigm in rats, we found that the activity of LDT cholinergic neurons and cholinergic transmission-from the LDT to VTA are critical for the acquisition and expression of cocaine CPP. Moreover, ex vivo electrophysiological analyses revealed that chronic cocaine administration induces plasticity in excitatory synaptic transmission and membrane excitability of LDT cholinergic neurons. Furthermore, noradrenaline, which is released from locus coeruleus axon terminals, attenuated inhibitory synaptic transmission in LDT cholinergic neurons which were obtained from rats that had received chronic cocaine but not saline administrations. This cocaine-induced plasticity in LDT cholinergic neurons may enhance the excitability of these neurons, resulting in changes in the reward circuit activity that might be associated with the development of addicted behaviors induced by cocaine.