Substance and alcohol actions/misuse最新文献

The 10-day administration of glutamine (500 mg/kg per day) with the drinking water to adult albino rats with different alcohol motivation resulted in a significant increase in the content of glutamate, GABA and taurine in the brain. The level of glycine was decreased only in the ethanol-preferring animals. The results obtained are discussed in terms of a possible role of the amino acid neurotransmitters, particularly GABA, in the antialcoholic action of glutamine.

The 3-aminobutane homolog (HMDA) of 3,4-methylenedioxyamphetamine (MDA) was synthesized and compared to MDA for acute pharmacologic/toxicologic properties in mice. The lethality of intraperitoneal doses of HMDA equalled or exceeded that of MDA, depending on whether mice were grouped or isolated after dosing. All deaths with HMDA occurred by 6 hours, while many were delayed to 6-24 hours for MDA, particularly in the aggregated condition. Rather similar response patterns were seen for the N-methylated derivatives of MDA and HMDA. Catecholaminergic receptor blockers, haloperidol, propranolol and phenoxybenzamine, which previously were found protective against MDA lethality, were ineffective against HMDA. However, phenoxybenzamine supplemented a protective action of phenobarbital toward HMDA lethality. The dose-related pattern of locomotor activity effects of HMDA differed from the one seen for MDA, which has been suggested to characterize hallucinogenic agents. Thus, HMDA differs qualitatively in actions from MDA and tends to be more toxic acutely for mice.

A computer-controlled device was used to deliver intravenous injections of saline or d-amphetamine, in patterns resembling those of animals trained to self-administer the drug via lever pressing. Amphetamine, administered in this manner (over the course of an 8 hr test session), induced a 27% decrease in brain norepinephrine. The injection of the amino acid precursor L-tyrosine (100 mg/kg) prior to sacrifice abolished the decrements in brain norepinephrine. In animals administered i.v. saline, L-tyrosine treatment did not alter brain norepinephrine concentrations. Earlier clinical studies have suggested that the norepinephrine reuptake inhibitor desipramine is useful in controlling psychomotor stimulant abuse (the rationale being that this agent compensates for reduced levels of the amine). If this hypothesis is correct, L-tyrosine may be a safer method to replenish cerebral norepinephrine pools.

Two groups of alcohol addicts (total of 14 subjects), were submitted to Traditional Manual Acupuncture and pituitary hormone plasma levels, including B-Endorphin (B-EP), were measured in basal condition and after 1, 5, 20 and 60 minutes from needle withdrawal. Group A patients had a polarity towards negative affective tone presenting signs of dysphoria while group B was composed of the so-called "social drinkers". No difference existed in basal hormonal values, except slightly elevated plasma B-EP levels in group A. No significant responses to TMA were recorded in plasma ACTH, Cortisol, Prolactin or GH levels in groups A and B. Social drinkers showed an increase of B-EP plasma levels in response to TMA (128 +/- 62.1%, mean +/- SD) which on the contrary was absent in dysphoric alcoholics (2.8 +/- 38.6%, p less than 0.01). The same was true for B-Lipotropin plasma levels. These preliminary results suggest that different fashions of alcohol abuse may be associated with different reactivity of the endogenous opioid system.

Barbiturate physical dependence was produced by twice-daily administration of Na barbital to cats according to the "low" dose barbiturate protocol (Okamoto et al., J. Pharmacol. Exp. Ther. 207: 906, 1978). The duration of treatment was 1, 2, 3, 5, 9 or 14 weeks. Pharmacodynamic tolerance was assessed by relating the degree of neurofunctional impairment to the blood barbital concentration at the time when the functional test was performed. Evaluation of withdrawal was based on whole-animal observation and subjective assessment of overt withdrawal signs. Motor activity and withdrawal convulsions were monitored continuously by an activity recording device. It was found that the pharmacodynamic tolerance and physical dependence continued to develop throughout the treatment period and no apparent ceiling on these phenomena was observed. The "low" level chronic dosing merely prolonged the time required to develop physical dependence of severity comparable to that produced by shorter durations of "high" level chronic dosing.

Brain proteins of BALB/cBy mice were labeled for a period of 8 days by a single intraperitoneal injection of valine. Following this the mice received 10% ethanol and protein breakdown was estimated from the release of label from brain proteins. Ethanol intake resulted in a significant inhibition of cerebral protein breakdown in vivo as measured in whole brain and in subcellular brain fractions (myelin, synaptosomes, mitochondria, microsomes, and nuclei). The intake of 10% ethanol for 4.5 months resulted in minor alterations in amino acid levels; increase in some and decrease in others were observed in plasma and brain, but most of the changes were not significant (P greater than 0.05). The uptake of AIB in brain was decreased 17% by prolonged ethanol intake.

We examined the effect of acute and chronic ethanol administration on brain and liver gamma-hydroxybutyric acid (GHB), the effect of pyrazole on the ethanol-GHB interaction, and the effect of acetaldehyde on brain and liver GHB. Ethanol produced a marked increase in liver GHB but had no effect on GHB in brain. The ethanol effect in liver was not blocked by pyrazole. Acetaldehyde had no effect in brain or liver on GHB.

The effects of betacarbolines on guinea-pig isolated sinus nodes superfused with Tyrode's solution at 35 degrees C were analyzed. All analogs depressed the automaticity. The phase 4 of transitional fibers was depressed, in the absence of any change in maximum diastolic potential. The threshold for harmaline action was 10(-7)M. Dehydrogeneration of harmaline into harmine increased the potency. Removal of the methoxy group (harmane) did not modify the potency but accelerated the recovery. Substitution of the methoxy group by a hydroxy group (harmalol and harmol) reduced markedly the potency of harmaline and harmine, respectively.

This report presents a set of findings from a three wave 36 month longitudinal study on the use of cigarettes, alcohol, marijuana/hashish and other drugs by a population of children and adolescents ranging in age from 9 to 17 at the time of first interview. Gross differences in percentages of subjects reporting using substances across the three data collection intervals are found to be quite small. However, when these differences are examined in detail, it is found that a good deal of initiation of use by some subjects and curtailing of use by others stands behind the relatively small net changes in use from one interval to another. Escalation in substance use, from less mood altering to more mood altering substances, is found to exist, but to appear far less frequently than "initial" multiple drug use. Finally, "intensity" of use of one substance is found to be somewhat related to age and very strongly related to the use of other substances. Limitations of findings due to episodic rather than continuous monitoring of substance use are noted.

Data from personal interviews and questionnaires were collected from alcoholics in treatment, alcoholism treatment agency directors and community gatekeepers. The health services utilization model proposed investigated individual predisposing factors; client attitudes and beliefs about alcohol, treatment, and health; client personal enabling traits; client social enabling characteristics; and structural characteristics of treatment services. Results discussed include the effects of structural characteristics of treatment agencies on alcoholic women's use of these agencies; gender specific differences in predisposing, personal enabling and social enabling factors and in attitudes and beliefs; ethnic differences among women in personal and environmental barriers to treatment; knowledge, attitudes and referral practices of community gatekeepers; and evaluation of workshop designed to train community gatekeepers to identify and refer alcoholics, particularly women alcoholics.