Effects of laterodorsal tegmentum excitotoxic lesions on behavioral and dopamine responses evoked by morphine and d-amphetamine.

Cholinergic and glutamatergic projections from the laterodorsal tegmental nucleus (LDT) in the rat pons excite midbrain dopamine cells to directly modulate forebrain dopamine transmission. We show that LDT-lesioned rats express higher intensity stereotypy (including orofacial movements), and higher levels of accumbal dopamine release in response to d-amphetamine (1.5 mg/kg), as compared to sham-operated rats. In contrast, LDT-lesioned rats showed decreased stereotypy and attenuated accumbal dopamine efflux as compared to sham animals, in response to morphine (2.0 mg/kg). These results suggest that the LDT plays a critical role in mediating motoric and neurochemical effects of diverse drugs of abuse, and that the pharmacology of the drug may critically determine whether its efficacy will be enhanced or attenuated by alterations in LDT activity. We conclude that the LDT has functional connections with the nigrostriatal dopamine system to affect drug-evoked stereotypy, which has implications for motoric disorders that are characterized by nigrostriatal dysfunction.