Kindling of the mesolimbic dopamine system: animal model of psychosis

In order to examine the behavioral and physiologic consequences of chronic activation of the mesolimbic dopamine system, the nucleus of origin in the ventral tegmental area was stimulated electrically for 2 seconds daily through chronically implanted intracranial electrodes in cats at the same point where instillation of the GABA blocking agent bicuculline induced a characteristic fear, staring, searching, and withdrawal response. None of the animals developed sustained after-discharge or seizures following daily stimulation for 2 months. Progressive fearfulness, hiding, loss of social behavior, and EEG spike or slow activity in the ipsilateral nucleus accumbens developed in three of six intact animals. Two cats with prior 6-hydroxydopamine lesions of catecholamine pathways did not develop behavioral change in response to local bicuculline or daily electrical stimulation of the ventral tegmental area but demonstrated pronounced after-discharge or EEG spike propagation during the kindling procedure.