Catecholamine systems as the neural substrate for intracranial self-stimulation: a hypothesis

The hypothesis was investigated that activation of central catecholamine (CA) systems is essential for intracranial self-stimulation (ICSS). Brain sites that support ICSS in the rat were found to be highly correlated with electrodes in 3 major CA systems: the mesolimbic and nigrostriatal dopaminergic systems and the dorsal noradrenergic system. Stimulation at ICSS loci in the brain stem causes release of catecholamines at terminals in ascending CA systems. Lesion studies show suppression of ICSS proportional to the degree of damage to the stimulated CA system. Drugs influence ICSS in accordance with their effects on transmission at dopaminergic and noradrenergic synapses. Enhancement of nicotinic-cholinergic mechanisms facilitates ICSS, but the effect requires that CA mechanisms be intact. Neurophysiological experiments suggest that two systems characterized by different axonal refractory periods are involved in ICSS. The data are insufficient to determine whether these correspond to the dopamine and norepinephrine systems. Norepinephrine has an inhibitory effect at many postsynaptic receptor sites, and ICSS is often accompanied by reduction or cessation of cellular discharges in NE terminal areas. Food ingestion has also been demonstrated to produce an inhibitory effect on cells in a noradrenergic terminal area. ICSS has been demonstrated in numerous species, including man, in brain areas that overlap considerably with loci whose stimulation supports ICSS in the rat. Stimulation of ICSS loci in man is commonly associated with verbal reports of intense pleasurable sensations.