Importance of hypothalamic function to stressor-induced responsiveness of the GABAA receptor in the cerebral cortex: a non-corticosterone influence.
Catecholamine terminals in the paraventricular nucleus (PVN) of the hypothalamus of 60-day-old rats were destroyed by the stereotaxic injection of 6-hydroxydopamine into the PVN (6-OHDA; 9 micrograms/1.5 microliters bilaterally), and the rats were tested 2 weeks later. Lesions led to a 70% reduction of norepinephrine in the hypothalamus and a loss of dopamine-beta-hydroxylase immunoreactivity in the PVN. Furthermore, 6-OHDA lesions in the hypothalamus disrupted stressor-induced (15 min of restraint) changes in GABAA receptor function in the cerebral cortex (assessed by measuring chloride-facilitated benzodiazepine binding) but did not alter stressor-induced increases in plasma corticosterone levels. Additionally, the lesion did not change the responsiveness of the GABAA receptor to the corticosterone metabolite, allotetrahydrodeoxycorticosterone. These results indicate that stressor-induced changes in cortical GABAA receptor function are not driven by the stressor-induced release of corticosterone. A separate group of animals were tested for behavioral responses to challenge, and while 6-OHDA-induced lesions did not alter total scores in the test of environment-specific social interaction, the lesions did induce a change in composition of the behavior. Lesioned animals demonstrated increased physical (vigorous contact) interactions, similar to behavior previously observed in younger rats. The results of the behavioral study support a role for the GABAA receptor in the cerebral cortex in mediating appropriate behavioral responses to challenge in the adult rat. Thus, a hypothalamic lesion that prevented challenge-induced changes in GABAA receptor function in the cortex (with no change in the corticosterone response to the stressor) also led to altered behavioral responses to challenge.
Department of Psychology, University of Rochester, NY 14627.
C K
CK
Kellogg
J R
JR
Inglefield
M K
MK
Taylor
G L
GL
Pleger
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000276:immunology / Q000378:metabolism; D007031:Hypothalamus / Q000502:physiology*; D007398:Interpersonal Relations; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*
D000777:Anesthetics; D002712:Chlorides; D011963:Receptors, GABA-A; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D016627:Oxidopamine; D004299:Dopamine beta-Hydroxylase; D003345:Corticosterone; D009638:Norepinephrine