Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.
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PMID:Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain. 170 Sep 26

Although cannabinoids exert strong effects on brain function, there have been no extensive analyses of the long-term effects of cannabinoids on mammalian brain structure. Consequently, we conducted quantitative light and electron microscopic studies on the brains of rats treated chronically with delta 9-tetrahydrocannabinol (THC) (5 X weekly for 8 months--approximately 30% of the life-span). In these studies, we found significant THC-induced changes in hippocampal structure: specifically, THC-treated animals exhibited decreased neuronal density and increased glial cell reactivity (i.e. an increase of cytoplasmic inclusions). In addition, we confirmed prior reports of THC-induced increases in adrenal-pituitary activity, since both adrenocorticotropic hormone (ACTH) and corticosterone were elevated substantially during an acute stress. However, the animals appeared to be only minimally affected behaviorally by the doses used (highest dose: 8 mg/kg) and no effects of THC were observed on several ultrastructural variables, including synaptic density. The observed hippocampal morphometric effects of chronic THC are similar to apparent glucocorticoid-dependent changes that previously have been found to develop in rat hippocampus during normal aging. Given that cannabinoids and steroids are similar in chemical structure in several respects, therefore, the present results seem to raise the possibility that chronic THC exposure may alter hippocampal anatomical structure by interactions with, or mimicry of, adrenal steroid activity.
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PMID:Quantitative changes in hippocampal structure following long-term exposure to delta 9-tetrahydrocannabinol: possible mediation by glucocorticoid systems. 283 17

The effect of acute (1 day) or subchronic (25 days) treatment with delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent of marihuana, on plasma norepinephrine (NE), epinephrine (E), corticosterone, beta-endorphin (beta-end), and splenic natural killer (NK) cell activity of the rat was studied. Groups of animals received subcutaneously, either THC in corn oil + saline (3 mg THC/kg); oil + saline; or THC + naloxone (2 mg naloxone/kg and 3 mg THC/kg). Acute injection of THC with or without naloxone did not significantly change plasma levels of NE, E corticosterone, beta-end, or the NK cell activity. However, subchronic treatment with THC significantly reduced plasma levels of NE, E, corticosterone, and NK cell activity, compared to controls. The plasma beta-end levels were significantly elevated in the THC-treated animals. In the THC + naloxone group of animals, the plasma hormone levels (corticosterone and beta-end) were similar to control levels and the NK cell activity was significantly higher than in THC-treated animals. These results indicate that subchronic exposure to THC results in suppression of splenic NK cell activity. The interaction of THC with the endogenous opiate system appears to be a contributing factor leading to the NK cell suppression in rats. A direct suppressive action of THC or its metabolites on the NK cell is not ruled out by this study.
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PMID:Effects of acute and subchronic delta 9-tetrahydrocannabinol administration on the plasma catecholamine, beta-endorphin, and corticosterone levels and splenic natural killer cell activity in rats. 299 13

The effect of chronic administration of delta 9-tetrahydrocannabinol (delta 9-THC) on the endogenous opiate and catecholamine levels was investigated. Intact male rats were injected daily either with vehicle (50 microliters oil) or delta 9-THC in oil (3 mg delta 9-THC/kg body wt). The treatments were administered subcutaneously over a period of 25 days. All animals were decapitated after the last injection and trunk plasma was assayed for prolactin, beta-endorphin-like immunoreactivity (beta-end LI), norepinephrine (NE), epinephrine (E), dihydroxyphenyl acetic acid (DOPAC) and dopamine (DA). The preoptic area (POA) and medial basal hypothalamus were assayed for methionine enkephalin, beta-endorphin and catecholamines. Chronic delta 9-THC treatment resulted in an increase in POA and MBH methioine-enkephalin and beta-end LI as well as an increase in plasma beta-end LI. The POA, MBH and plasma NE and E levels were lower in these animals when compared with the controls. In the MBH, however, the delta 9-THC treated rats contained higher DA and DOPAC levels when compared with the controls. These results support our view that chronic delta 9-THC administration alters the activities of the endogenous opiate system as well as the catecholaminergic system and consequently impairs the endocrine functions.
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PMID:Effect of chronic administration of delta 9-tetrahydrocannabinol on the endogenous opioid peptide and catecholamine levels in the diencephalon and plasma of the rat. 609 37

The ability of cannabinoids to affect anterior pituitary luteinizing hormone (LH) secretion has been largely attributed to a central nervous system site of action, however, the mechanism(s) by which cannabinoids alter LH release remains unclear. In the present study, the acute administration of delta-9-tetrahydrocannabinol (THC) produced a dose-related suppression of plasma LH and stimulation of adrenocorticotropin (ACTH) levels in ovariectomized female rats. To determine if activation of the hypothalamic-pituitary-adrenal axis was involved in the ability of THC to inhibit LH release, female rats were either pretreated with the corticotropin-releasing hormone (CRH) receptor antagonist, alpha-helical CRH, or were adrenalectomized prior to acute THC administration, in order to assess the roles of CRH and corticosterone in the ability of THC to suppress LH secretion. A low dose of THC (0.5 mg/kg b.w., iv) produced a decrease in plasma LH levels at 20 and 40 min posttreatment in ovariectomized, sham adrenalectomized rats. However, in adrenalectomized animals, plasma LH levels were suppressed at 40 min and remained decreased at 80 min following THC administration. Thus, the duration of LH suppression following THC treatment was significantly increased in adrenalectomized versus sham adrenalectomized rats (p < 0.05). Furthermore, pretreatment with the CRH receptor antagonist, alpha-helical CRH (100 micrograms/5 microliters, icv), 30 min before THC administration, attenuated the ability of a high THC dose (1.0 mg/kg) to inhibit LH release in ovariectomized rats. Together, these results demonstrate that THC has significant effects on LH and ACTH secretion in ovariectomized rats and suggest that THC-induced CRH activation, but not corticosterone release, plays a role in the suppression of LH release by cannabinoids.
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PMID:Role of the hypothalamic-pituitary-adrenal axis in the suppression of luteinizing hormone release by delta-9-tetrahydrocannabinol. 920 7

Marijuana and its cannabinoid constituents have profound effects on anterior pituitary hormone secretion. Exposure to delta 9-tetrahydrocannabinol inhibits gonadotropin, prolactin, growth hormone, and thyroid-stimulating hormone release and stimulates the release of corticotropin. Consequently, cannabinoid exposure could have profound effects on the function of the reproductive system, lactation, metabolism, and on the endocrine stress axis. The acute effects of cannabinoids on the endocrine system are consistent with its actions on brain neurotransmitter systems involved in the regulation of neuropeptides that modulate anterior pituitary hormone secretion. Although cannabinoid receptors appear to play a major role in the ability of cannabinoids to influence hormone release, much remains to be learned concerning their function in the neuroendocrine regulation of hormone secretion.
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PMID:Function of cannabinoid receptors in the neuroendocrine regulation of hormone secretion. 997 76

beta-Endorphin is an endogenous opioid that produces behavioral effects similar to heroin and morphine and is released in the nucleus accumbens by cocaine, amphetamine and ethanol, suggesting a general involvement in the reinforcing effects of abused drugs. Here we show that, in rats, Delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, produces large increases in extracellular levels of beta-endorphin in the ventral tegmental area and lesser increases in the shell of the nucleus accumbens. We then used a two-lever choice THC-discrimination procedure to investigate whether THC-induced changes in endogenous levels of beta-endorphin regulate the discriminative effects of THC. In rats that had learned to discriminate injections of THC from injections of vehicle, the opioid agonist morphine did not produce THC-like discriminative effects but markedly potentiated discrimination of THC. Conversely, the opioid antagonist naloxone reduced the discriminative effects of THC. Bilateral microinjections of beta-endorphin directly into the ventral tegmental area, but not into the shell of the nucleus accumbens, markedly potentiated the discriminative effects of ineffective threshold doses of THC but had no effect when given alone. This potentiation was blocked by naloxone. Together these results indicate that certain psychotropic effects of THC related to drug abuse liability are regulated by THC-induced elevations in extracellular beta-endorphin levels in brain areas involved in opiate reward and reinforcement processes.
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PMID:Beta-endorphin elevations in the ventral tegmental area regulate the discriminative effects of Delta-9-tetrahydrocannabinol. 1521 74