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 Chronic (10 or 20 mg/kg i.p. daily for 10 days and withdrawn 24 h prior, chronic DMI) and acute (10 mg/kg, i.p. + 60 min prior, acute DMI) desipramine treatments abolished physostigmine (0.5 mg/kg i.p.)-induced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