Functional reactivity of central cholinergic systems following desipramine treatments and sleep deprivation.
This study examined the effects of acute and chronic desipramine, 24-h total sleep deprivation (TSD) and 96-h REM sleep deprivation (REMSD) on physostigmine-induced hypothermia, analgesia and behaviour. The effects of acute and chronic desipramine treatment on oxotremorine-induced hypothermia were also examined. Intraperitoneal administration of physostigmine (0.5 mg/kg i.p.) induced hypothermia, analgesia, purposeless chewing movements (chewing) and head tremors. While atropine given in a low dose (1.0 mg/kg i.p. 15 min prior) did not antagonize the hypothermia, chewing and head tremor associated with physostigmine (0.5 mg/kg i.p.), a higher dose of atropine (10 mg/kg i.p. 15 min prior) decreased physostigmine-induced hypothermia, chewing and head tremor behaviour. Chronic (10 or 20 mg/kg i.p. daily for 10 days and withdrawn 24 h prior, chronic DMI) and acute (10 mg/kg, i.p. + 60 min prior, acute DMI) desipramine treatments abolished physostigmine (0.5 mg/kg i.p.)-induced hypothermia compared with saline pretreatment. Interestingly atropine (1 mg/kg i.p. 15 min prior) reversed the inhibitory effect of chronic DMI on hypothermia induced by physostigmine. Acute but not chronic DMI decreased physostigmine-induced chewing and head tremor behaviour. Atropine (1 mg/kg i.p. 15 min prior) increased the inhibitory action of acute DMI on physostigmine-induced chewing behaviour. Acute DMI (10 mg/kg i.p.) decreased oxotremorine (0.1 mg/kg i.p.)-induced hypothermia, while chronic DMI increased the hypothermic effect of oxotremorine. TSD and REMSD did not alter physostigmine (0.5 mg/kg i.p.)-induced hypothermia; however, REMSD and stress decreased physostigmine-induced analgesia and chewing.It is suggested that chronic desipramine treatment decreased physostigmine-induced hypothermia by causing hypersensitivity of pre-synaptic muscarinic receptors, whereas acute desipramine decreased the sensitivity of post-synaptic muscarinic receptors
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000698:Analgesia; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced; D007274:Injections, Intraperitoneal; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012892:Sleep Deprivation / Q000503:physiopathology*; D013239:Stereotyped Behavior / Q000187:drug effects; D013315:Stress, Psychological / Q000503:physiopathology; D014202:Tremor / Q000139:chemically induced
D018759:Adrenergic Uptake Inhibitors; D018721:Muscarinic Agonists; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D010095:Oxotremorine; D010830:Physostigmine; D003891:Desipramine