Reversal of Morphine Tolerance after Medial Thalamic Lesions in the Rat

Teitelbaum, Herman; Catravas, George N.; McFarland, Willard L.

doi:10.1126/science.185.4149.449

Cited by 42 publications

(12 citation statements)

References 3 publications

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“…Reported use of morphine results in the development of dependence and tolerance t o the drug. It has been shown that lesions in the limbic structures, hypothalamic nuclei, and MTh can result in a complete or partial loss of tolerance to the opiates [31,32,47,49]. In the present investigation, all the reports concerning the site of morphine action were taken into consideration and electrodes were inserted in structures related to motor coordination, analgesia, temperature regulation, and in central sites where 5HT, NE, and DA are synthesized.…”

Section: Discuss1 Onmentioning

confidence: 99%

Effects of morphine on sensory‐evoked responses recorded from central gray, reticular formation, thalamus, hypothalamus, limbic system, basal ganglia, dorsal raphe, locus ceruleus, and pineal body

Dafny

Marchand

McClung

et al. 1980

J of Neuroscience Research

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Field potential recordings of acoustic and photic-evoked responses were obtained from 15 brain sites of freely behaving unanesthetized rats previously implanted stereotaxically with permanent electrodes. Several dosages of morphine (1, 5, 10, 30, and 50 mg/kg) were examined. The activities recorded from all the structures in this study, except the cochlear nucleus (CoN), were affected by morphine. Different sensitivities to morphine threshold were observed between structures, and several structures exhibited dose-related patterns (ventromedial hypothalamus (VMH), caudate nuucleus (CN), central gray (CG), hippocampus (Hipp), and lateral septum (Spt)). Several brain sites, after the initial dose of morphine, did not recruit more responses to subsequent doses of the drug, ie, exhibited all-or-none responses (pineal body (PB), medial thalamus (MTh), anterior hypothalamus (AH), mesencephalic reticular formation (MRF), and the dorsal raphe (DR)). In some structures, morphine induced increases in the response amplitudes, while in other sites decreases in response amplitudes were elicited. Biphasic responses, ie, increases in response amplitude after low doses of the drug and decreases in response amplitude after higher dosages, were also observed (VMH, CN, DR, CG, and MRF). The acoustic-evoked responses were affected by morphine more than the photic responses. The present observations indicated that 1) morphine exerts effects in many parts of the central nervous system (CNS); 2) some structures are more sensitive to morphine than others; 3) only a few structures exhibit dose-related patterns and, thus, may represent sites of direct morphine action; 4) some structures exhibit all-or-none responses; and 5) morphine depressed activity in some structures and increased activity in others, ie, morphine elicited different effects in different structures.

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Section: Discuss1 Onmentioning

confidence: 99%

Effects of morphine on sensory‐evoked responses recorded from central gray, reticular formation, thalamus, hypothalamus, limbic system, basal ganglia, dorsal raphe, locus ceruleus, and pineal body

Dafny

Marchand

McClung

et al. 1980

J of Neuroscience Research

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“…Recently some investigators have suggested that the medial thalamus is an important brain site involved in the development of tolerance to the EEG effects of morphine (Teitelbaum, Catravas & McFarland, 1974) and the naloxone-precipitated abstinence syndrome in the rat (Wei, Loh & Way, 1973a and b). It (Shute & Lewis, 1967) which projects diffusely to the cortex and releases ACh in this region.…”

Section: Introductionmentioning

confidence: 99%

Morphine–naloxone Interaction in the Central Cholinergic System: The Influence of Subcortical Lesioning and Electrical Stimulation

Jhamandas

Sutak

1976

British J Pharmacology

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I The opiate antagonist naloxone, injected or topically applied to the cerebral cortex, had no significant effect on the spontaneous output of cortical acetylcholine (ACh) in rats. 2 Morphine (2.5 mg/kg) administered intravenously inhibited the release of cortical ACh. A subsequent injection of naloxone rapidly reversed morphine-induced inhibition, and produced a sustained increase in the release of ACh. Topical application of naloxone solutions, after morphine, produced a slow and weak reversal of its inhibitory action. 3 Destruction of the medial thalamus abolished both the inhibitory effects of morphine on the cortical ACh release, and its antagonism by naloxone administered after the agonist. 4 Injection of naloxone in a low dose (0.1 mg/kg) increased the release of cortical ACh provoked by electrical stimulation of either the medial thalamus or the reticular formation in normal rats. In the morphine-dependent rat, naloxone also facilitated the evoked release and its action was greater than in control animals. The facilitatory effect of naloxone on the cortical release evoked by stimulation of the medial thalamus was greater than its effect on the release evoked by stimulation of the reticular formation in both normal and morphine-dependent rats. Naltrexone, a narcotic antagonist, also facilitated the electrically stimulated release of cortical ACh. 6 It is suggested that (a) morphine and naloxone act at a subcortical site, probably the medial thalamus, to modify the cortical ACh release and that (b) naloxone may facilitate the electricallyinduced release of ACh in the CNS by antagonizing the effect of the endogenous morphine-like factor, enkephalin.

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“…Since the manifestation of opiate withdrawal is dependent upon the activity of several discrete brain areas [Kerr and Pozuelo, 1971;Teitelbaum et al, 1974;Laschka et al, 19761, these results indicate that rIFN-a has direct neuromodulatory activity. However, in lieu of our previous studies upon systemically administered rIFN-a and withdrawal severity, it is evident that i.c.v.…”

Section: Results Experiments Amentioning

confidence: 99%

Immune response products alter CNS acitivity: Interferon modulates central opioid function

Dafny¹,

Lee²,

Dougherty³

1988

J of Neuroscience Research

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The present report provides evidence to support the hypothesis that peptides released during an immune response alter CNS activity and thus may provide a means for the immune system to transmit afferent signals into the brain. Specifically, it is demonstrated that recombinant interferon-alpha (rIFN-alpha), a peptide associated with the immune response to viral infection, can alter opiate withdrawal severity in a dose-dependent manner upon direct injection into brain areas essential for this phenomenon. These results are compared and contrasted with the effect of systemically injected rIFN-alpha upon opiate withdrawal. In addition, an electrophysiological investigation into the basis of the interaction of opioids and rIFN-alpha in brain structures essential for the expression of opioid activities is also presented. Finally, the effects of rIFN-alpha upon the functions of both the CNS and other systems is discussed in terms of the effects reported for other peptides associated with immune responses.

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Reversal of Morphine Tolerance after Medial Thalamic Lesions in the Rat

Abstract: Tolerance, manifested by a diminished electroencephalographic response at cortical and subcortical recording sites, was found in rats subjected to repeated systemic injections of morphine sulfate. Reversal of tolerance to morphine resulted from destruction of the medial thalamus.

Cited by 42 publications

References 3 publications

Effects of morphine on sensory‐evoked responses recorded from central gray, reticular formation, thalamus, hypothalamus, limbic system, basal ganglia, dorsal raphe, locus ceruleus, and pineal body

Effects of morphine on sensory‐evoked responses recorded from central gray, reticular formation, thalamus, hypothalamus, limbic system, basal ganglia, dorsal raphe, locus ceruleus, and pineal body

Morphine–naloxone Interaction in the Central Cholinergic System: The Influence of Subcortical Lesioning and Electrical Stimulation

Immune response products alter CNS acitivity: Interferon modulates central opioid function

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