Endorphins in Psychiatry

Verebey, Karl

doi:10.1001/archpsyc.1978.01770310083006

Cited by 132 publications

(5 citation statements)

References 127 publications

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“…Numerous clinical observations support the involvement of the opioid system in the morbidity of depression (Verebey et al, 1978; Gold et al, 1982). Animal studies have shown that acute morphine administration increases immobility in the forced swim test (Amir, 1982; Zurita and Molina, 1999) and water wheel test (Kastin et al, 1984).…”

Section: Discussionmentioning

confidence: 98%

Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation

Ide

Takahashi

Takamatsu

et al. 2016

IJNPPY

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Background:Opioid and dopamine systems play crucial roles in reward. Similarities and differences in the neural mechanisms of reward that are mediated by these 2 systems have remained largely unknown. Thus, in the present study, we investigated the differences in reward function in both µ-opioid receptor knockout mice and dopamine transporter knockout mice, important molecules in the opioid and dopamine systems.Methods:Mice were implanted with electrodes into the right lateral hypothalamus (l hour). Mice were then trained to put their muzzle into the hole in the head-dipping chamber for intracranial electrical stimulation, and the influences of gene knockout were assessed.Results:Significant differences are observed between opioid and dopamine systems in reward function. µ-Opioid receptor knockout mice exhibited enhanced intracranial electrical stimulation, which induced dopamine release. They also exhibited greater motility under conditions of “despair” in both the tail suspension test and water wheel test. In contrast, dopamine transporter knockout mice maintained intracranial electrical stimulation responding even when more active efforts were required to obtain the reward.Conclusions:The absence of µ-opioid receptor or dopamine transporter did not lead to the absence of intracranial electrical stimulation responsiveness but rather differentially altered it. The present results in µ-opioid receptor knockout mice are consistent with the suppressive involvement of µ-opioid receptors in both positive incentive motivation associated with intracranial electrical stimulation and negative incentive motivation associated with depressive states. In contrast, the results in dopamine transporter knockout mice are consistent with the involvement of dopamine transporters in positive incentive motivation, especially its persistence. Differences in intracranial electrical stimulation in µ-opioid receptor and dopamine transporter knockout mice underscore the multidimensional nature of reward.

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Section: Discussionmentioning

confidence: 98%

Distinct Roles of Opioid and Dopamine Systems in Lateral Hypothalamic Intracranial Self-Stimulation

Ide

Takahashi

Takamatsu

et al. 2016

IJNPPY

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“…These data indicate that NT shares several characteristics with both neuroleptic agents such as haloperidol and chlorpromazine on the one hand, and with opiates such as morphine and 3-endorphin on the other hand. The impprance of these observations is underscored by the recent hypotheses postulating a role for endorphins and other opiate peptides in the regulation of behavioral states including mental disorders (25)(26)(27)(28). The precise role and action of NT in the modulation of neural transmission and its subsequent expression in alterations of physiological and behavioral processes remain obscure.…”

Section: Discussionmentioning

confidence: 99%

Alterations in nociception and body temperature after intracisternal administration of neurotensin, beta-endorphin, other endogenous peptides, and morphine.

Nemeroff¹,

Osbahr²,

Manberg³

et al. 1979

Proc. Natl. Acad. Sci. U.S.A.

136

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The antinociceptive and hypothermic effects of intracisternal administration of 11 endogenous neuropeptides and morphine were evaluated in mice. Of the substances tested, only neurotensin (NT) and l-endorphin exerted significant antinociceptive and hypothermic effects; NT was the most potent in inducing hypothermia whereas l-endorphin was the most potent antinociceptive agent via this route of administration.Both NT and f3-endorphin were, on a molar basis, considerably more potent antinociceptive agents than morphine, [Metlenkephalin, or [Leujenkephalin. NT-induced analgesia and hypothermia both were significantly dose-dependent. Substance P was found to produce significant hyperalgesia and hyperthermia. Bombesin produced a significant hypothermic effect, whereas somatostatin and luteinizing hormone-releasing hormone (luliberin) produced hyperthermia. None of the other peptides studied [bradykinin, thyrotropin- In recent years, several peptides endogenous to brain have been found to produce various effects when administered either systemically or directly into the central nervous system (1, 2). Considerable attention has been focused on the endorphins and enkephalins which are endogenous opiate-like peptides that produce antinociception (3-5), hypothermia (6), and various other behavioral effects (7). In addition, they bind avidly to brain opiate receptors (8). Neurotensin (NT) and bombesin are potent hypothermic agents after intracerebroventricular administration in rats and mice (9, 10). Furthermore, peptides other than the endorphins and enkephalins have been reported to produce significant analgesia after direct intracerebral injection. These include NT, bradykinin, and substance P (11)(12)(13)(14).The purpose of the present study was to evaluate the antinociceptive properties and the effect on colonic temperature of 11 endogenous neuropeptides and morphine after intracisternal administration in mice. Of particular interest was the evaluation of the dose-response relationship of NT-induced antinociception. MATERIALS AND METHODSAntinociceptive activity was measured in adult male albino Swiss-Webster mice (25-30 g) by the tail-immersion test developed for use in rats by Janssen and coworkers (15) as modified for use in mice by Sewell and Spencer (16). Groups of mice (n > 6 per group) were lightly anesthetized with ether and injected intracisternally with vehicle (0.9% NaCl, pH 7.5) or with one of the following peptides: NT, substance P, thyrotropin-releasing factor (thyroliberin), luteinizing hormone-releasing factor (luliberin), bradykinin, melanocyte-stimulating hormone-release inhibiting factor (melanostatin), somatostatin, 3-endorphin, [Met]enkephalin, [Leu]enkephalin, and bombesin. Morphine sulfate was also tested. Thyroliberin (lot 31-330-AL) was provided by Abbott; NT (lot 14-296-10), f-endorphin (lot 28-111-30), and bombesin (lot 42-206-20) were generously supplied by Jean E. Rivier (The Salk Institute, La Jolla, CA). All the other peptides and morphine were purchased commercially: luliberin...

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“…Drug-subculture theory does not directly incorporate the pharmacological effects of drugs in predicting relapse, but it is compatible with perspectives such as Wikler's (1953) conditioning theory, and recent theories of endorphins and drug metabolism (Verebey et al 1978). These perspectives hold that the drugs consumed alter body and brain biochemistry and metabolism so that a person who has previously been a heavy user or was physically dependent upon a substance will exhibit physical or psychological dependence (Lindesmith 1947;Chein et al 1964;Eddy et al 1965) and will seek out and return to drug use as previously.…”

Section: Johnsonmentioning

confidence: 99%