Supraspinal and spinal mediation of naloxone-induced morphine withdrawal in rats

Marshall, Dennis C.; Buccafusco, Jerry J.

doi:10.1016/0006-8993(85)90518-9

Cited by 47 publications

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References 23 publications

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“…The importance of the spinal cord in mediating autonomic symptoms of withdrawal is underscored by the observation that 2 consecutive withdrawal pressor responses of equal magnitude could be elicited when the first injection of naloxone was administered into the lateral ventricle and the second into the intrathecal space. Conversely, once the spinal cord was withdrawn, a second withdrawal response could not be elicited by injection of naloxone via any other route of administration (Marshall and Buccafusco, 1985b).…”

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confidence: 99%

“…In addition, marked behavioral and autonomic withdrawal symptoms are also observed following intrathecal (i.t.) injection at the level of the spinal sympathetic outflow (Marshall and Buccafusco, 1985b). The importance of the spinal cord in mediating autonomic symptoms of withdrawal is underscored by the observation that 2 consecutive withdrawal pressor responses of equal magnitude could be elicited when the first injection of naloxone was administered into the lateral ventricle and the second into the intrathecal space.…”

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

Marshall¹,

Jj²

1987

J. Neurosci.

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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 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-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

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

Marshall¹,

Jj²

1987

J. Neurosci.

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“…Withdrawal from spinal opioids, experimentally induced by naloxone, will typically induce a pressor response in rats 48 . Supraspinal sites may mediate a more intense pressor response to naloxone than caudal sites, while other cardiovascular and behavioral signs of withdrawal are mediated exclusively via spinal cord pathways 64,65 . This redundancy may allow for different medications to ameliorate different signs and symptoms of withdrawal.…”

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Intentional Intrathecal Opioid Detoxification in 3 Patients: Characterization of the Intrathecal Opioid Withdrawal Syndrome

et al. 2012

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This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature.

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“…The autonomic disturbances during opiate withdrawal include cardiovascular changes which are characterized by increased blood pressure and changes in heart rate (Himmelsbach 1941, Buccafusco 1983). The 479 increase in blood pressure has previously been interpreted as the effect of a generalized activation of the sympathetic nervous system (Buccafusco 1983, Marshall & Buccafusco 1985 although, to our knowledge, no direct evidence of an increased sympathetic nerve activity has been presented. However, in a previous study we have shown, by means of direct sympathetic nerve recordings, that the blood pressure increase during naloxone-precipitated morphine withdrawal is accompanied by a marked inhibition of renal sympathetic nerve activity in both conscious and anaesthetized animals (Delle & Thoren 1987).…”

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Renal sympathetic nerve activity during morphine abstinence in sino‐aortic baroreceptor‐denervated rats

Delle

Ricksten

Thorén

1988

Acta Physiologica Scandinavica

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This study was undertaken to investigate the influence of the arterial baroreceptors on the response of renal sympathetic nerve activity (rSNA) during naloxone-precipitated morphine abstinence in rats. In chronically baroreceptor-denervated, morphine-dependent rats, rSNA, mean arterial pressure (MAP) and heart rate (HR) were studied before and after repeated i.v. bolus doses of naloxone (0.005-5 mg kg-1), during chloralose anaesthesia or in the conscious state. In the anaesthetized animals, naloxone doses of 0.05-5 mg kg-1 caused a pronounced inhibition of rSNA, reaching a level 61% below pre-naloxone activity. This was accompanied by increases in MAP and HR. In the conscious rats, the lower doses of naloxone elicited an initial state of increased somatomotor activity. This was paralleled by slight increases in rSNA and MAP. After 4-5 min, the behavioural excitation faded and was replaced by lethargy. The rats exhibited still signs of withdrawal in the form of piloerection, chromodacryorrhoea and defaecations. Concomitantly, rSNA returned towards the pre-naloxone level, while MAP showed a sustained increase. The higher naloxone doses exacerbated the hypertension without any further changes in rSNA or in behaviour. We conclude that the influence of the baroreceptors is of minor significance for the inhibition of rSNA during naloxone-precipitated abstinence in anaesthetized rats. In conscious, intact rats, however, the baroreceptors seem to contribute to rSNA inhibition since no significance decrease of rSNA occurred in baroreceptor-denervated rats in the present study. This is in contrast to our previous finding of a marked inhibition of rSNA in rats with intact baroreceptors.

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Supraspinal and spinal mediation of naloxone-induced morphine withdrawal in rats

Cited by 47 publications

References 23 publications

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

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

Intentional Intrathecal Opioid Detoxification in 3 Patients: Characterization of the Intrathecal Opioid Withdrawal Syndrome

Renal sympathetic nerve activity during morphine abstinence in sino‐aortic baroreceptor‐denervated rats

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