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)

Immunoreactive beta-endorphin (IR-BE) was measured in the plasma, anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL) and hypothalamus of male rats treated chronically (once daily for ten days) with cocaine. Cocaine produced a consistent elevation in the concentration of IR-BE in the plasma, the AP and the NIL at doses of 2.5 - 20 mg/kg/ip. The release of IR-BE from the AP and the NIL was determined in vitro and was found to be increased by treatment with cocaine. Chronic administration of cocaine did not affect the concentration of IR-BE in the hypothalamus. Chromatographic analysis revealed that cocaine produced a slight decrease in the amount of beta-endorphin relative to beta-lipotropin in the AP. Beta-endorphin was the major form of IR-BE released by the AP and the sole constituent and secretory product of the NIL. These data indicate that chronic administration of cocaine stimulates the endogenous opiate system, elevating the levels of IR-BE in the pituitary and promoting beta-endorphin release.
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PMID:Cocaine influences beta-endorphin levels and release. 296 43

Cocaine is known to affect different brain systems, particularly those associated with arousal, motor and motivational functions. In order to identify a possible neurochemical link among these systems, we investigated the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist and dissociative anesthetic, ketamine (as a mixture with the sedatives acepromazine and xylazine) on the secretion of pituitary adrenocorticotropin hormone (ACTH) and on the development of behavioral sensitization induced by cocaine. Pretreatment with the ketamine anesthetic mixture (1.6 ml/kg; s.c.) completely blocked the stimulation of ACTH by cocaine (5 mg/kg, i.v.; administered 30 min after the ketamine mixture) without interfering with ACTH secretion induced by exogenous corticotropin-releasing factor (CRF; 5 micrograms/kg; i.v.) or interleukin-1 beta (IL-1 beta; 100 ng/kg; i.v.). Administration of the ketamine mixture prior to each of five repeated cocaine injections (15 mg/kg; i.p.) also completely reversed the behavioral sensitization observed in saline-treated control animals. Administration of the anesthetic mixture did not appear to impair the dopamine (DA) re-uptake blocking properties of cocaine in the nucleus accumbens since substantial increases in extracellular DA were observed in the presence of the ketamine mixture. In addition to the present results, no behavioral sensitization was also observed in rats anesthetized with a different general anesthetic (pentobarbital, 50 mg/kg) under similar conditions to that of the ketamine mixture. Taken together, these results are in accordance with the hypothesis that stimulation of excitatory amino acid receptor function may be just one of the mechanisms whereby cocaine exerts its effects on neuroendocrine and behavioral activating systems.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A ketamine mixture anesthetic inhibits neuroendocrine and behavioral consequences of cocaine administration. 780 43

Neuroendocrine pharmacology represents a potentially valuable approach to the assessment of alterations in neuronal function in the brain of human cocaine abusers. Neuroendocrine effects of the monoamine uptake inhibitor cocaine have predominantly been examined in laboratory animals. These preclinical studies may help to identify the optimal challenge tests to be performed in clinical studies. In laboratory animals, acute administration of cocaine activates the hypothalamic-pituitary-adrenal axis, via actions on serotonergic and dopaminergic neurons in the brain. Cocaine also reduces prolactin secretion, probably by dopaminergic mechanisms, although the necessary studies to confirm this hypothesis have not been performed. Cocaine also reduces renin secretion, and increases vasopressin and luteinizing hormone secretion, by mechanisms which have not been clearly established. The adrenocorticotropin, corticosterone, prolactin, and renin responses to cocaine are generally unaltered by prior cocaine exposure, suggesting that tolerance or sensitization to the endocrine effects of cocaine does not occur. However, several studies have determined that prior cocaine exposure alters the serotonergic regulation of hormone secretion. Chronic cocaine exposure reduces some of the hormone responses to the serotonin (5-HT) releasers p-chloroamphetamine and d-fenfluramine, suggesting deficits in the functional status of serotonergic nerve terminals. Additionally, repeated cocaine exposure produces subsensitive 5-HT1A-mediated hormone responses, and supersensitive 5-HT2-mediated responses. Alterations in dopaminergic- or noradrenergic-mediated hormone responses have not been examined in animals chronically exposed to cocaine. Endocrine studies in human cocaine abusers have largely examined basal hormone levels or the hormone responses to cocaine. Strong conclusions from these studies are limited because (1) many neuronal and nonneuronal systems regulate secretion of each hormone, so that alterations in basal hormone levels cannot be attributed to only one neurotransmitter; and (2) hormone responses to cocaine cannot be examined in cocaine-naive subjects due to ethical considerations, making it impossible to determine whether the response in cocaine abusers is abnormal. It may be more beneficial for studies in cocaine abusers to examine the hormone responses to drugs that specifically affect monoaminergic neurons and compare the data with cocaine-naive individuals.
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PMID:Monoaminergic regulation of neuroendocrine function and its modification by cocaine. 781 44

Cocaine is reported to be immunotoxic. The biochemical mechanisms responsible for the immunopharmacological outcomes of cocaine in vivo and in vitro remain, however, to be fully elucidated. Our experimental data confirm that exposure of normal human T cells to micromolar concentrations of cocaine modulates T-cell responses to stimulation by a variety of stimuli, and indicate that cocaine impairs early activation events during CD4+ but not CD4- T-cell stimulation. Pre-incubation of enriched CD4+ T-cell subpopulations that express the homing receptor CD62L with nanomolar concentrations of the endogenous opioid peptide beta-endorphin leads to a more severe impairment of activation than that noted following pre-incubation with micromolar concentrations of cocaine alone. These findings begin to elucidate the molecular and cellular mechanisms of the immunopathology of cocaine. Our data support the proposition that cocaine abuse may place cocaine-abuser HIV-seropositive individuals at increased risk of opportunistic infections.
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PMID:Cocaine blunts human CD4+ cell activation. 785 54

Cocaine (COC) has been described as exerting potent stimulatory effects on the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study, we investigated the acute and chronic effects of intracerebroventricular and intrahypothalamic injections of COC in rats. Twenty minutes following intracerebroventricular injection of COC (1-100 micrograms), dose-dependent increases in plasma corticosterone (CS) were observed, although the highest dose tested (100 micrograms) evoked a significantly smaller response than that following 50 micrograms. Prior stressing of the animals resulted in elevated plasma CS levels (315 +/- 16 ng/ml) and significantly decreased plasma CS concentrations following 50 micrograms COC (87.8 +/- 3.2%). Injections above the hypothalamic paraventricular nucleus (PVN), the site of corticotropin-releasing-factor-secreting neurons which regulate HPA activity, required relatively higher doses of COC in order to elicit increases in plasma CS; injections of 0.5 microgram had no effect, 1 microgram resulted in an increase to 168 +/- 68 ng/ml (p < 0.005), and 2.5 micrograms produced an increase to 146 +/- 29 ng/ml (p < 0.025). Post-PVN injections of COC, behind the posterior margin of the PVN in the vicinity of the ventral noradrenergic ascending bundle, also required a high dose (2.5 micrograms) in order to elicit a plasma CS response (208 +/- 19 ng/ml; p < 0.005), with no significant response seen following 0.5 microgram COC. No effects of specific neurotoxic lesions of the catecholaminergic or serotonergic innervation of the hypothalamus were observed upon adrenocortical responses to COC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intracerebroventricular and intrahypothalamic cocaine administration on adrenocortical secretion. 847 16

Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis in rodents and in humans. This study examined the acute effects of cocaine (0.4 and 0.8 mg/kg) and saline placebo on pulsatile adrenocorticotropic hormone (ACTH) and cortisol release in seven male rhesus monkeys. Pulsatile ACTH and cortisol release were evaluated with an intensive (2-min) venous blood sampling procedure and cluster analysis. In addition, the behavioral responses to cocaine were analyzed to assess the relationship between HPA axis activation and behavior. Although analysis of group data revealed significant (P < .05) increases in pulse amplitude and incremental peak height of ACTH and cortisol release after cocaine (0.8 mg/kg) administration, examination of individual data indicated that this effect was not consistent across all monkeys. Cocaine (0.8 mg/kg) increased ACTH plasma levels within 4.7 +/- 1.3 min (P < .05) and amplitude-related characteristics (P < .05) of pulsatile ACTH and cortisol release only in those animals that subsequently showed behavioral stimulation (high responders: n = 3). The frequency of pulsatile ACTH and cortisol remained unchanged by cocaine. Cocaine (0.8 mg/kg) decreased the mean amplitude of ACTH peaks with no changes in pulsatile cortisol release in the four monkeys that showed no behavioral stimulation (low responders). These differences in pulsatile ACTH and cortisol release patterns after cocaine could not explained by different plasma cocaine levels. Peak plasma cocaine levels averaged 63.1 +/- 13.4 and 78.0 +/- 21.4 ng/ml within 2 min after lower dose and 183.3 +/- 52.3 and 204.3 +/- 50.8 ng/ml after higher dose of cocaine in high- and low responder groups, respectively (P > .05; N.S.). Base-line cortisol, but not ACTH, levels were higher (P < .05) in low responders before administration of 0.8 mg/kg of cocaine. Peak and valley characteristics of base-line cortisol release were higher in low responders than in high responders and an inverse relationship was found between basal cortisol levels and postcocaine ACTH release and behavior. In summary, cocaine stimulated the pulsatile ACTH and cortisol release by increasing the amplitude of secretory episodes in behaviorally responsive monkeys.
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PMID:Effects of cocaine on pulsatile activity of hypothalamic-pituitary-adrenal axis in male rhesus monkeys: neuroendocrine and behavioral correlates. 861 24

Lewis (LEW) and Fischer 344 (F344) rats differ in responsiveness of the hypothalamo-pituitary-adrenocortical (HPA) axis as well as in their behavioral responses to drugs of abuse. The present experiments were conducted to compare hypothalamic corticotropin-releasing factor (CRF), plasma adrenocorticotropic hormone (ACTH) and plasma corticosterone (CS) responses to cocaine (0-60 mg/kg, i.p.) in LEW and F344 rats. Acute administration of cocaine resulted in decreases in CRF and dose-related increases in CS and ACTH with significant differences observed between the strains. Cocaine also increased plasma norepinephrine concentrations. Although the CS response was increased in the F344 compared to LEW rats, the percent change in the CS response was markedly enhanced in LEW rats. Plasma ACTH concentrations as well as the percentage of the control response were dramatically increased at the 40 mg/kg cocaine dose in the LEW compared to F344 rats. Since cocaine-induced changes in HPA axis activity may contribute to behavioral responses to cocaine, another experiment was performed to compare the locomotor responses to novelty and to acute cocaine between LEW and F344 rats. Strain differences were not observed in the locomotor response to novelty or to cocaine. These data indicate that strain differences exist in the neuroendocrine response to acute cocaine exposure.
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PMID:Differential neuroendocrine and behavioral responses to cocaine in Lewis and Fischer rats. 883 60

The hypothalamic-pituitary-adrenal (HPA) axis plays a role in cocaine dependence and major depressive disorder. The authors examined the correlation between baseline depressive symptomatology and pituitary-adrenal axis activation induced by acute cocaine challenge. Twelve patients with cocaine dependence were administered an iv bolus of cocaine (0.6 mg/kg) and their plasma was assayed for levels of adrenocorticotropic hormone (ACTH) and cortisol. Depressive symptomatology was assessed with total Hamilton rating scale for depression (HRSD) scores and its vegetative and cognitive superfactors. Cocaine produced a mean increase from baseline of 261% for ACTH and 73% for cortisol plasma levels. Changes in ACTH (r=0.69) and cortisol (r=0.59) were positively and significantly correlated with total HRSD scores and its vegetative, but not cognitive, factor symptom cluster. These results suggest that the HPA axis may be involved in affective disturbances associated with the use of cocaine. Implications of these data for the pathophysiology of cocaine dependence are discussed.
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PMID:Depressive symptomatology and cocaine-induced pituitary-adrenal axis activation in individuals with cocaine dependence. 1046 91

The product of the DARPP-32 gene mediates intracellular signals initiated by the binding of dopamine to its receptors. Cocaine administration leads to increased activation of dopamine receptors, and causes activation of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis. We determined the effects of chronic 'binge' pattern cocaine on HPA activity in mice containing a targeted disruption of the DARPP-32 gene. Mice received three daily injections of cocaine (15 mg/kg/injection) for 14 days, and were sacrificed 30 min after the last injection. We measured the levels of plasma adrenocorticotropin (ACTH) and corticosterone which reflect HPA activity. In wild-type controls, 'binge' cocaine administration significantly increased plasma ACTH and corticosterone levels. In contrast, DARPP-32-deficient mice failed to show a significant elevation of either plasma ACTH or corticosterone levels following 'binge' cocaine. The results indicate that DARPP-32 plays a role in mediating the stimulatory effects of cocaine on the HPA axis.
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PMID:Effects of chronic 'Binge' cocaine administration on plasma ACTH and corticosterone levels in mice deficient in DARPP-32. 1051 82

Cocaine stimulates the release of adrenocorticotropin hormone (ACTH) and cortisol in both clinical and preclinical studies, but the temporal sequence of cocaine-induced changes in other hormones and affective states is unclear. The purpose of this study was to analyze the pattern and temporal concordance of cocaine-induced changes in ACTH, cortisol, dihydroepiandrosterone (DHEA), epinephrine, heart rate and subjective reports of euphoria. Six healthy men who met Diagnostic and Statistical Manual-IV (DSM-IV) criteria for cocaine abuse provided informed consent for participation. Cocaine (0.4 mg/kg) or saline placebo was infused intravenously over 1 min under double-blind conditions. Euphoria, ACTH, epinephrine and heart rate increased significantly within 8 to 12 min after i.v. cocaine administration in all subjects (P<0.01-0.001). Moreover, the increases in euphoria, ACTH, epinephrine and heart rate each were significantly correlated with increases in plasma cocaine levels (P<0.001). Euphoria increased significantly within 2 min after i.v. cocaine injection, as plasma cocaine levels were increasing, and peak euphoria was reported at 10 min (P<0.001). Peak ACTH values were measured at 8.7 (+/-0.8) min after cocaine injection (P<0.01). Peak levels of epinephrine were measured at 10 (+/-1) min after cocaine injection (P<0.05). Peak increases in heart rate occurred at 11.7 (+/-1.1) min after cocaine injection (P<0.05). Peak levels of cortisol and DHEA were measured at 36 (+/-4.0) and 28.7 (+/-4.3) min after cocaine injection (P<0.01 and P<0.01). The temporal concordance between cocaine-induced stimulation of ACTH, epinephrine and subjective euphoria suggests that these hormonal changes are significant concomitants of the abuse-related effects of cocaine. The similarities between these hormonal profiles, the subjective effects of cocaine and the effects of "stress" are discussed.
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PMID:Temporal concordance of cocaine effects on mood states and neuroendocrine hormones. 1175 Jul 70


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