Substance and alcohol actions/misuse最新文献

Mild to moderate heroin addicts started on ambulatory detoxification with methadone were sublingually treated with placebo or desglycinamide9-arginine8-vasopressin (DGAVP, 1 mg/day) for 5 days using a double-blind design. Treatment with DGAVP (6 patients) led to a longer time course of clinic attendance and resulted in a higher percentage of successful detoxifications as compared to placebo treatment (6 patients). The analyses of urine samples revealed that DGAVP treatment decreased the use of heroin and cocaine below that with placebo treatment. The medical attendant judged DGAVP treatment superior to placebo treatment. It is concluded that treatment with DGAVP during the initial phase of methadone detoxification of heroin addicts may facilitate detoxification. This beneficial effect of DGAVP is consistent with animal data showing that this peptide may attenuate the reinforcing qualities of heroin.

Nicotine potentiates, in a dose dependent manner, the sleep time induced by sodium pentobarbital but not by ethanol. Mecamylamine, a nicotinic receptor antagonist, blocked the nicotine induced increase in sleep time. Atropine itself reduced sleep time but did not change the nicotine effect. It is hypothesized that the central and the peripheral nicotinic receptors play an important role in potentiating sodium pentobarbital induced sleep time.

The present study was undertaken to determine if the effects of delta 9-tetrahydrocannabinol on gonadotropin secretion are mediated through endogenous opioid neurons in the rat. Ovariectomized rats were treated with estradiol-benzoate (EB, day O) and with progesterone (P) at 11:00 h on day 2. At 13:00 h (day 2), these estradiol primed and progesterone-treated (EBP) animals received either delta 9-THC (3mg/kg in oil, i.m.); naloxone (Nal) 3 mg/kg in saline, s.c.) or delta 9-THC + Nal. All animals were decapitated at 16:00 h and trunk sera were assayed for luteinizing hormone (LH) and prolactin (Prl), while medial basal hypothalami (MBH) were assayed for luteinizing hormone-releasing hormone (LHRH). Naloxone enhanced the EBP-induced hypersecretion of LH by 2-fold while delta 9-THC completely blocked the EBP-induced secretion of LH. delta 9-THC slightly diminished the stimulatory effect of Nal on LH secretion and caused a 2-fold increase in serum Prl concentrations, while Nal did not influence the serum PRL levels in these EBP rats. However, Nal did block the stimulatory effects of delta 9-THC on Prl secretion. delta 9-THC caused a significant increase in MBH content of LHRH, an effect which was prevented by Nal. These results suggest that the inhibitory effects of delta 9-THC on serum LH and the stimulatory effect of the cannabinoid on Prl are mediated by an opioid mechanism.

The paper considers the rational biological basis for treatment of alcohol withdrawal reactions, alcoholic hallucinosis and the Wernicke-Korsakoff syndrome. Both clinical and experimental data indicate that the alcohol withdrawal reaction reflects a state of hyper-reactivity of the central nervous system. The evidence comprises physiological, electrophysiological and biochemical findings. Magnesium, vitamins and antipsychotics are not specific in the treatment of the alcohol withdrawal reactions per se; rational treatment comprises drugs that may substitute for the suppressive effects of alcohol in the CNS during readaptation to the alcohol free condition (e.g. barbiturates or benzodiazepines). Alcoholic hallucinosis is characterised by acutely developed auditory hallucinations of an evil or reproachful nature. The condition may develop during or shortly after excessive alcohol consumption in chronic alcoholics. Suggestibility and unclear consciousness is not part of the condition. Tentatively three subgroups are suggested to occur: a) a withdrawal reaction; treatment with sedatives is recommended; the prognosis is good, b) a toxic reaction occurring during the drinking bout; this condition should be treated with antipsychotics until symptoms have disappeared. The prognosis is fairly good, c) a schizophreniform condition. Long-term treatment with antipsychotics must be applied. The Wernicke-Korsakoff syndrome is described. The condition often occurs during or shortly after an acute withdrawal reaction. The biochemical role of the etiological factor thiamine in glucose metabolism suggests that precautions (thiamine treatment) must be taken when giving a glucose load to alcoholics. Finally focus is set on the recent suggestion that the syndrome may in some cases result from an inborn enzymatic abnormality comprising low binding of thiamine pyrophosphate to transketolase. Psychobiological aspects of treatment in alcoholism may apply to a very large spectrum of conditions involving symptoms of cerebral, hepatic, gastrointestinal, cardial and peripheral nervous system origin. In the present expose we shall concentrate on organic cerebral reactions partly or exclusively presenting with psychiatric symptoms and signs. Thus the review will consider the rational biological basis for treatment of alcohol withdrawal reactions (including delirium tremens), alcoholic hallucinosis and the Wernicke-Korsakoff syndrome.

Gonadectomy resulted in a gradual increase in plasma gonadotropin levels in female mice. At certain intervals after ovariectomy, a single administration of delta 9-tetrahydrocannabinol (THC; 50 mg/kg) reduced plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), while at other times THC had no effect. Administration of THC significantly reduced plasma concentrations of LH and FSH in intact diestrous females. In an additional study, in intact diestrous females injected with testosterone propionate (TP; 125 micrograms), concommitant exposure to THC did not affect plasma testosterone (T) levels, but plasma dihydrotestosterone (DHT) levels at 20 and 60 min were significantly higher in animals receiving TP and THC. Administration of THC can alter pituitary gonadotropin release in intact diestrous and in ovariectomized female mice. Effects of THC on plasma androgen levels after exogeneous treatment with TP suggest that THC can alter metabolism or target tissue response to gonadal steroids.

This paper reviews several attempts to demonstrate state-dependent (St.D) effects from alcohol and reports a study in which the subject's state (sober or intoxicated) produces a 'dissociation' decrement in recall performance only when the drug state differed from that under which the original learning took place. Thirty-two subjects were used in a 2 x 2 design with moderate doses of alcohol (mean BAC = 81 mg/100 ml). In a second study, with 16 volunteers, alcohol was administered immediately after learning in order to distinguish between 'stimulus' and 'storage' hypotheses. Greater retention was found for those subjects whose drug states were the same in memory consolidation and retrieval. Thus, an alcohol state effective during the memory consolidation interval following acquisition appears to be a sufficient condition for producing St.D learning. In this context, St.D learning might be better termed state-dependent memory storage and retrieval. The implications of these results for the aetiology and treatment of alcohol dependence are discussed.

Considerable evidence has accrued over the preceding two decades to establish that ethanol is a gonadal toxin. In the male such toxicity is both direct, being expressed at the level of the hypothalamus and/or pituitary. Moreover, such toxicity is due in part to direct ethanol exposure and also in part to the consequences of ethanol metabolism (e.g., acetaldehyde generation, redox changes and alterations in enzyme levels and activities). Thus as a result of studies performed both in man and in animals, it has been shown conclusively that ethanol abuse per se, and not the associated liver disease that occurs with alcohol abuse, is responsible for the impotence, loss of libido, and testicular atrophy which are seen commonly in chronic alcoholic men. With prolonged alcohol abstinence, recent studies have suggested that spontaneous recovery of normal sexual function is possible in some chronic alcoholic men if testicular atrophy has not yet occurred and if their responses to clomiphene and/or luteinizing hormone releasing factor stimulation are normal. In contrast, abstinent alcoholic men with either overt testicular atrophy or inadequate responses to such pharmacologic challenges fail to recover despite continued alcoholic abstinence. Such men will require either a penile prosthesis or long-term oral androgen therapy to achieve "acceptable" sexual functioning. Considerably less information is available concerning the adverse effects of ethanol and alcohol abuse in women. The available data however, suggests that women, like men, develop gonadal injury as a consequence of alcohol abuse and that such injury occurs both at the level of the ovary and at the level of the hypothalamus and pituitary.

This paper reviews the clinical, epidemiologic, and empirical work on the offspring effects of intrauterine alcohol exposure, including fetal alcohol syndrome, incorporating some of the latest studies from several countries.

To see if UDP accelerates the metabolism of ethanol, Wistar female rats were given UDP(100 mg/kg b.w.) intra-gastrically prior to a single dose of ethanol (3 g/kg b.w.) ingestion. UDP pretreatment accelerated blood ethanol disappearance rate by 50% (mg/kg animal/hr) by Widmark formula. Increases of the hepatic triglyceride concentration 6 hours and 20 hours after ethanol administration were significantly low in UDP pretreated animals suggesting the lipotropic effect of UDP. Neither the activity of alcohol dehydrogenase nor microsomal ethanol oxidizing system was affected by UDP pretreatment. The ratio of lactate to pyruvate in liver 6 hours after ethanol was not changed as compared with that of the control whether the rats were pretreated with UDP or not. There were significant increases in hepatic ATP content and the size of the adenylate pool in UDP pretreated group, whereas the energy charge was unchanged as compared with ethanol-alone group. These data suggest that UDP enhances ethanol metabolism possibly by causing a change in ATP metabolism.

The effect of ethanol on the anti-inflammatory actions of indomethacin was studied using carrageenan-induced edema in the paw of the rat as the test for acute inflammation. The agents were administered 1 hour prior to carrageenan injection, and the volume of the paw was measured immediately and at 3 and 5 hours after carrageenan. Ethanol at 1, 2, and 4 g/kg and indomethacin at 5 and 20 mg/kg significantly inhibited paw edema at 3 and 5 hours. The combination of the various doses of ethanol and indomethacin produced the same degree of inhibition as ethanol alone and significantly higher inhibition than indomethacin alone. The concentration of indomethacin in the inflammed paw was significantly higher than in the other paw in animals receiving 20 mg/kg indomethacin alone and 5 or 20 mg/kg indomethacin in combination with 2 g/kg ethanol. Ethanol co-administration significantly increased the concentration of indomethacin in the inflammed paw. Whether the observed interaction is due to increased concentration of indomethacin at the site of action or to direct interaction of ethanol and indomethacin in the inflammation process remains unclear.