title: Adaptive changes in alpha-2 adrenoceptor mediated responses: analgesia, hypothermia and hypoactivity.
abstract: The acute effects of the alpha-2 adrenoceptor agonists, clonidine and guanfacine, upon antinociception, hypothermia and motor activity were compared under conditions of receptor antagonism, denervation, and chronic administration of a tricyclic antidepressant compound. The analgesic actions of clonidine and guanfacine were antagonised by idazoxan, an alpha-2 receptor antagonist, but potentiated by pretreatment with the noradrenaline neurotoxin DSP4, and attenuated by chronic treatment with desipramine (DMI). Clonidine- and guanfacine-induced hypothermia was antagonised by idazoxan, potentiated by prior treatment with DSP4 and attenuated by chronic administration with DMI. Both clonidine and guanfacine produced decreases in motor activity that were attenuated by idazoxan but unaffected by prior DSP-4 treatment. Chronic DMI administration also attenuated clonidine-induced hypoactivity but potentiated guanfacine-induced hypoactivity. These diverse results describe both similar and differential adaptive mechanisms modulating the functional effect of alpha-2 receptor systems in the central nervous system.
authors.affiliation: Astra Pain Control and Research Centre, Södertälje, Sweden.
authors.forename: B G
authors.initials: BG
authors.lastname: Minor
authors.forename: W
authors.initials: W
authors.lastname: Danysz
authors.forename: G
authors.initials: G
authors.lastname: Jonsson
authors.forename: A K
authors.initials: AK
authors.lastname: Mohammed
authors.forename: C
authors.initials: C
authors.lastname: Post
authors.forename: T
authors.initials: T
authors.lastname: Archer
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007036:Hypothermia, Induced; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D006146:Guanidines; D006993:Hypnotics and Sedatives; D010648:Phenylacetates; D011942:Receptors, Adrenergic, alpha; D016316:Guanfacine; D003000:Clonidine; D003891:Desipramine