Chronic but not acute treatment with antidepressants enhances the electroconvulsive seizure response in rats.

The effects of the chronic administration of antidepressants on threshold electroconvulsive (ECS) seizures were evaluated in rats. Initially, tonic-clonic seizures were induced in 90% of the animals. Of those animals responding with tonic-clonic seizures, 42% had hindlimb extension (extensors); the remainder showed only hindlimb flexion (flexors). No alteration in the pattern of seizures was observed 24 hr after a single oral dose of any of the antidepressant drugs. The rats were then treated with a total of 20 consecutive daily doses of antidepressants and threshold electroconvulsive seizure responses were evaluated 24 hr after the last dose. A significantly greater percentage of rats responded with extensor seizures after chronic treatment with amoxapine, chlorimipramine, parglyine and mianserin. There was no change in the pattern of seizures of the rats treated chronically with desipramine, but the duration of the clonic phase was reduced. After a 7 day period free of drugs a significantly greater percentage of animals had extensor seizures in the groups treated with amoxapine, chlorimipramine, pargyline and desipramine but not mianserin. In the light of evidence that chronic treatment with antidepressants reduces the activity of norepinephrine- or isoproterenol-sensitive adenylate-cyclase, and that the norepinephrine system is an important endogenous anticonvulsant factor in electroconvulsive seizures, these results suggest that the same mechanism may mediate both the therapeutic and proconvulsant effects of the chronic administration of antidepressants.

cis-Flupentixol antagonism of the rat prefrontal cortex neuronal response to apomorphine and ventral tegmental area input.

This study was designed to characterize the response of a select population of prefrontal cortex neurons to exogenous and endogenous dopaminergic influences. Of particular interest were neurons with efferent projections to the ventral tegmental area (VTA) which are part of a reciprocal innervation between the prefrontal cortex and the VTA. Extracellular single unit recording techniques were used to determine the response of cortical neurons to electrical stimulation of the VTA in chloral hydrate anesthetized rats. The neurons were selected on the basis of their electrophysiological characteristics (large amplitude with positive initial deflection) and were classified as to whether or not they were antidromically activated from the VTA. Apomorphine (25 micrograms/kg, IV) significantly reduced the spontaneous activity of both the antidromically identified and the unidentified prefrontal cortex neurons. The apomorphine (25 micrograms/kg, IV) response was antagonized by cis-flupentixol (1.0 mg/kg, IV) in both antidromically identified and unidentified cortical neurons. Stimulation of the VTA also induced a synaptically mediated inhibition of the cortical neuron spontaneous activity. The orthodromic VTA stimulus-evoked inhibition was antagonized by cis-flupentixol (1.0 mg/kg, IV) for both the antidromically identified and the unidentified neurons (63 and 71% of the neurons respectively). The results indicate that a select population of prefrontal cortex neurons respond specifically to exogenous and endogenous dopaminergic influences and that the response is independent of efferent projections to the VTA.