[Cocaine and disturbances of adrenergic neurotransmission]

Cocaine releases peripheral and central stores of catecholamines and their plasma concentration increases in very significantly under the influence of the drug. One also observes a vaso-constriction of cerebral and coronary arteries. Decreases in blood flow through those vessels have been observed in cocaine addicts examined with the magnetic resonance and positron emission tomography techniques. Some of these changes may still be present 15 days after withdrawal. The authors suggest an hypothesis to account for the general mode of action of cocaine. The synaptic increase in catechol produced by this drug is calcium dependent and would induce an "up regulation" of receptor proteins of calcium channels with increased calcium intracellular fluxes. There would be an increase in catecholamine neuronal turnover and synthesis not a depletion. Conversely the adrenergic post-synaptic receptors would undergo a "down regulation". Such impairment of adrenergic neurotransmission is associated with an increase in Angiotensin II release and a decreased GABA activity. Sensory stimuli resulting from this impairment induce a dominant memory associated with drug seeking and consuming behavior.