title: Evidence for altered alpha 2-adrenoceptor function following isolation-rearing in the rat.
abstract: This study investigated central alpha 2-adrenoceptor function in differentially reared rats. Rats reared from weaning were either housed singly or in groups of five. Measurements of spontaneous ambulatory activity at 4 weeks postweaning showed that isolates were more hyperactive on exposure to a novel environment than grouped rats. alpha 2-Adrenoceptors were investigated using alpha 2-adrenoceptor agonist-induced behaviours, [3H]-idazoxan binding and measurement of forskolin-stimulated cyclic AMP accumulation. Clonidine (0.001-1.0 mg/kg IP) induced mydriasis in both groups with no difference observed in the response between the isolation and group-reared animals. Clonidine (0.01-0.5 mg/kg IP) induced hypoactivity in both groups, with the effect significantly greater in the isolation-reared rats. Idazoxan markedly attenuated both responses, confirming their induction by alpha 2-adrenoceptor stimulation. Clonidine-induced hypoactivity and mydriasis are mediated by pre- and postsynaptic alpha 2-adrenoceptors, respectively; therefore the results suggest rats reared in isolation have enhanced presynaptic but unchanged postsynaptic alpha 2-adrenoceptor function. Saturation binding experiments using [3H]-idazoxan were undertaken to determine alpha 2-adrenoceptor number (Bmax) and affinity (Kd) in membranes prepared from the frontal cortex and hippocampus. Analysis of binding data revealed an increase in receptor number in the hippocampus of isolates. Cyclic AMP accumulation was measured in hippocampal slices from differentially reared rats. Isolation-rearing did not affect cyclic AMP accumulation in response to stimulation by forskolin (30 microM). However, the selective alpha 2-adrenoceptor agonist, UK14304, produced a significantly greater inhibition of cyclic AMP accumulation in slices from isolated rats, confirming changes in alpha 2-adrenoceptor function following isolation rearing.
authors.affiliation: Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Fulford
authors.forename: S
authors.initials: S
authors.lastname: Butler
authors.forename: D J
authors.initials: DJ
authors.lastname: Heal
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
authors.forename: C A
authors.initials: CA
authors.lastname: Marsden
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000493:pharmacokinetics / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004146:Dioxanes / Q000493:pharmacokinetics / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D019329:Idazoxan; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011680:Pupil / Q000187:drug effects; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D012934:Social Isolation; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D018341:Receptors, Adrenergic, alpha-2; D000242:Cyclic AMP; D003000:Clonidine; D019329:Idazoxan