title: Metabotropic glutamate receptor-mediated signaling dampens the HPA axis response to restraint stress.
abstract: Glutamate is an important neurotransmitter in the regulation of the neural portion of hypothalamus-pituitary-adrenal (HPA) axis activity, and signals through ionotropic and metabotropic receptors. In the current studies we investigated the role of hypothalamic paraventricular group I metabotropic glutamate receptors in the regulation of the HPA axis response to restraint stress in rats. Direct injection of the group I metabotropic glutamate receptor agonist 3,5-dihydroxyphenylglycine (DHPG) into the PVN prior to restraint leads to blunting of the HPA axis response in awake animals. Consistent with this result, infusion of the group I receptor antagonist hexyl-homoibotenic acid (HIBO) potentiates the HPA axis response to restraint. The excitatory effect of blocking paraventricular group I metabotropic glutamate signaling is blocked by co-administration of dexamethasone into the PVN. However, the inhibitory effect of DHPG is not affected by co-administration of the cannabinoid CB1 receptor antagonist AM-251 into the PVN. Together, these results suggest that paraventricular group I metabotropic glutamate receptor signaling acts to dampen HPA axis reactivity. This effect appears to be similar to the rapid inhibitory effect of glucocorticoids at the PVN, but is not mediated by endocannabinoid signaling.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Division of Pediatric Rehabilitation, United States. Electronic address: Nathan.evanson@cchmc.org.
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Evanson
authors.affiliation: University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D019540:Area Under Curve; D003345:Corticosterone / Q000097:blood; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012149:Restraint, Physical; D013997:Time Factors
chemical_list: D018683:Excitatory Amino Acid Agents; D018094:Receptors, Metabotropic Glutamate; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Glucocorticoids; Glutamate; HPA axis; Metabotropic; Rats; Stress