Involvement of the laterodorsal tegmental nucleus in the locomotor response to repeated nicotine administration

The locomotor altering properties of nicotine depend on activation of nicotinic acetylcholine receptors in the ventral tegmental area (VTA). The laterodorsal tegmental nucleus (LDTg) provides a significant proportion of the cholinergic innervation of the VTA. We tested the hypothesis that the locomotor effects of nicotine depend on the functional integrity of the LDTg. The spontaneous locomotor activity of LDTg and sham-lesioned control rats was measured over seven sessions, after which we examined the effects of repeated injections of nicotine in a day on-day off design, giving injections of saline on the nicotine-off days. Spontaneous locomotor activity was significantly lower in LDTg lesioned compared to control rats. LDTg lesions also blunted the effects of nicotine: control rats showed an initial locomotor depression after nicotine, but on repeated testing showed a progressive increase in the amount of locomotion in response to drug challenge. LDTg lesioned rats showed no differences in responding to nicotine compared to saline. These data show that the functional integrity of the LDTg is required in order to show normal locomotor response to nicotine. One explanation for this is that loss of the LDTg affects synaptic activity in the VTA.