Spinal cholinergic neurons and the expression of morphine withdrawal symptoms in the rat

DC Marshall, JJ Buccafusco
1987 Journal of Neuroscience  
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. lntrathecal (i.t.) administration of 1 pg carbachol or 5 ccg neostigmine resulted in increases in mean anterial pressure (MAP) of 32 and 45 mm Hg, respectively, in conscious, freely moving rats. The
more » ... or 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-l ), 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 hemicholinium3 (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 pg) produced a 14 mm Hg increase in MAP that was significantly augmented (21 mm Hg) following i.t. pretreatment with HC-3. These results may be explained by the presence of a descending spinal cholinergic pathway that facilitates the autonomic component of morphine withdrawal and an intrinsic spinal cholinergic pathway that is inhibitory to the expression of withdrawal. In drug-dependent rats, there is a significant pressor response associated with morphine withdrawal following systemic injection of the narcotic antagonist naloxone. Behavioral and autonomic signs of withdrawal can be elicited following the intraarterial (i.a.) injection (Buccafusco, 1983) of naloxone, as well as by injection of naloxone into localized areas of the CNS. For example, injection of naloxone into the lateral or fourth cerebral
doi:10.1523/jneurosci.07-03-00621.1987 pmid:3559705 fatcat:dl2qwufjsjewlk62t55xtbsoza