Anxiolytic properties of amygdaloid kindling unrelated to benzodiazepine receptors.
We investigated the possibility that repeated electrical stimulation of the basolateral amygdala (kindling) would increase punished behavior, a pre-clinical indicator of anti-anxiety activity. Male Sprague-Dawley rats, prepared with electrodes in the left basolateral nucleus and frontal cortex, were trained to bar-press under a multiple schedule in which either every 30th response produced food (no punishment) or every 10th response produce both food and a brief electric shock (punishment). Rates of punished responding were less than 10% of non-punished values. Brief electrical stimulation of the amygdala occurred biweekly, and the current levels were incremented from subconvulsive values (50 microA) to suprathreshold levels (150 microA). Electrical stimulation increased punished responding without concomitant changes in nonpunished behavior; increases were most pronounced in fully-kindled rats. Fully-kindled animals also demonstrated the largest primary afterdischarge. Electrical stimulation of the frontal cortex induced similar seizure and convulsive patterns but did not increase punished responding. Anxiolytic activity of amygdaloid stimulation was not prevented by the selective benzodiazepine antagonist Ro 15-1788, which antagonized similar behavioral effects of chlordiazepoxide. Thus, kindling of seizures in the amygdala results in behaviorally and neuroanatomically specific antianxiety actions which do not depend upon receptor sites blocked by Ro 15-1788 (benzodiazepine receptors).
Witkin
J M
JM
Preclinical Pharmacology, NIDA Addiction Research Center, Baltimore, MD 21224.
Lee
M A
MA
Walczak
D D
DD
D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology*; D002540:Cerebral Cortex / Q000502:physiology; D002707:Chlordiazepoxide / Q000494:pharmacology; D004558:Electric Stimulation; D005442:Flumazenil / Q000494:pharmacology; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*
D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide