Effect of Nicotine on Dynamic Function of Brain Catecholamine Neurons

Abstract

Burst firing in the mesolimbocortical dopamine (DA) neurons, originating in the ventral tegmental area (VTA), is facilitated by systemic administration of nicotine. Pharmacological results show that bursting in VTA-DA cells is critically dependent on a tonic, excitatory amino acid drive, probably originating from the medial prefrontal cortex. Cold inactivation of the prefrontal cortex caused pacemaker-like firing of VTA-DA cells, an effect partly antagonized by systemic nicotine. Clinically, hypofrontality has been associated with negative symptoms in chronic schizophrenia and with chronic alcoholism. Thus, smoking may provide a means to partially restore the dynamics of the VTA-DA system in such disorders. Intravenous nicotine also induces a selective activation of bursting in noradrenaline neurons of the pontine nucleus locus ceruleus. Pharmacological and physiological experiments clearly suggest that this effect is indirect, e.g. peripherally elicited and relayed to the locus ceruleus through its excitatory amino acid input from the paragigantocellular nucleus. The locus ceruleus activation is rapid in onset, dose dependent, short lasting and can be repeated within minutes. This effect of nicotine, which would imply an instant coping response, may be relevant to nicotine dependence, particularly in depressive states.