Potential locus and mechanism of blockade of conditioned avoidance responding by neuroleptics.
In order to assess the possible loci of action of neuroleptics in blocking the acquisition of a one-way conditioned avoidance response, microinjections of three neuroleptics and seven putative neurotransmitters were made into several brain regions and their effects on this behavior were assessed. When injected into the amygdala, the ED50 values for haloperidol (0.128 nmol), chlorpromazine (1.04 nmol) and thioridazine (1.41 nmol) were appropriate in relation to their clinical potency. Injections of neurotransmitters were without effect except in a few cases. Most significantly, the intra-amygdaloid administration of glutamate diethyl ester (an antagonist at quisqualate-type receptors) produced a blockade of avoidance acquisition which, as in the case of the neuroleptics, was not diminished by pretreatment with atropine. Following intraperitoneal injection of chlorpromazine, a statistically-significant blockade of avoidance acquisition and of glutamate, released from slices of amygdala, was obtained at doses of 2 mg/kg or more. With haloperidol, comparable behavioral effects and release of glutamate were found at doses of 0.05 mg/kg or more. The depression of release of glutamate from amygdaloid slices could be attributed to glutamate derived from glutamine. These data suggest a possible role for glutamatergic transmission in the effects of neuroleptics.
D000679:Amygdala / Q000502:physiology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D002746:Chlorpromazine / Q000494:pharmacology; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D005973:Glutamine / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D013881:Thioridazine / Q000494:pharmacology
D014150:Antipsychotic Agents; D005971:Glutamates; D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D006220:Haloperidol; D013881:Thioridazine; D002746:Chlorpromazine