Spinal cholinergic neurons and the expression of morphine withdrawal symptoms in the rat.
Behavioral and autonomic signs of the morphine withdrawal syndrome were measured in dependent rats injected with the opiate antagonist naloxone. The purpose of this study was to determine whether spinal cholinergic pathways play a role in the expression of spinally mediated withdrawal symptoms. Intrathecal (i.t.) administration of 1 microgram carbachol or 5 micrograms neostigmine resulted in increases in mean arterial pressure (MAP) of 32 and 45 mm Hg, respectively, in conscious, freely moving rats. The pressor response to carbachol began almost immediately after injection, but that to neostigmine was delayed in onset. Both responses were completely abolished following i.v. injection of 2 mg/kg atropine. However, in spinal-transected (C-1), ventilated rats, i.t. injection of carbachol or neostigmine resulted in only small, transient increases in MAP. Intraarterial (i.a.) injection of 0.5 mg/kg naloxone to morphine-dependent rats resulted in an immediate increase in MAP (to 33 mm Hg) that lasted at least 1 hr. This was accompanied by classical behavioral signs of withdrawal. Pretreatment of dependent rats with i.t. injection of atropine or hemicholinium-3 (HC-3) significantly reduced the pressor and several behavioral responses elicited by naloxone. In contrast, when morphine-dependent, spinal-transected rats were pretreated with i.t. injection of cholinergic antagonists, i.a. injection of naloxone resulted in an enhanced MAP response. Finally, in intact dependent rats, i.t. injection of naloxone (6 micrograms) produced a 14 mm Hg increase in MAP that was significantly augmented (21 mm Hg) following i.t. pretreatment with HC-3.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002319:Cardiovascular System / Q000503:physiopathology; D003655:Decerebrate State; D006426:Hemicholinium 3 / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000503:physiopathology*; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D010277:Parasympathomimetics; D006426:Hemicholinium 3; D009270:Naloxone; D009020:Morphine