Nicotine-induced catecholamine synthesis after lesions to the dorsal or ventral noradrenergic bundle

The role of projections from coerulear (A6) and lateral tegmental (A1-A5) noradrenergic cell groups in the induced catecholamine response to (-)-nicotine was studied following lesions to the dorsal (DNAB) or ventral (VNAB) noradrenergic bundle by 6-hydroxydopamine. The lesions produced large reductions in basal noradrenaline levels in hippocampus (after DNAB lesions) and hypothalamus (after VNAB lesions), while not affecting basal levels of dopamine or 5-hydroxytryptamine. Vehicle and sham operated controls showed a significant increase in DOPA accumulation in response to (-)-nicotine (0.8 mg/kg s.c.) following inhibition of amino acid decarboxylase. In DNAB lesioned rats, the response induced by (-)-nicotine in both the hippocampus and hypothalamus was significantly attenuated, whereas in VNAB lesioned rats the induced response was still evident. The effect of (-)-nicotine was also studied in the nucleus accumbens and was found not to be affected by either lesion. These data suggest that increases in catecholamine synthesis in the hippocampus and hypothalamus reflect increased noradrenaline synthesis, and that this effect occurs specifically in noradrenergic projections originating in the locus coeruleus.