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At least 199 records · Page 11Linked to original sources
PubMed1997

Repeated administration intensifies the reinforcing effect of fencamfamine in rats.

1. In the present study, we evaluated the role of repeated administration on conditioning place preference (CPP) induced by fencamfamine (FCF) in male rats. 2. Repeated FCF (3.5 mg/kg) or saline once or daily for ten consecutive days enhanced sniffing duration and decreased locomotion and rearing duration. 3. At the 3.5 mg/kg dose, FCF produced a significant place-preference effect. 4. Repeated exposures to FCF intensified its reinforcing properties. 5. These results suggest that repeated FCF administration sensitizes its rewarding effects, as with other addictive substances.

Animals↗
PubMed1998

Serotonin transporter messenger RNA in the developing rat brain: early expression in serotonergic neurons and transient expression in non-serotonergic neurons.

Serotonin has been shown to affect the development of the mammalian nervous system. The serotonin transporter is a major factor in regulating extracellular serotonin levels. Using in situ hybridization histochemistry the rat serotonin transporter messenger RNA was localized during embryogenesis, the first four weeks postnatally and adulthood. Three general classes of serotonin transporter messenger RNA expression patterns were observed: (i) early detection with continued expression through adult age, (ii) transient expression colocalized with vesicular monoamine transporter 2 messenger RNA but with no detectable tryptophan hydroxylase immunoreactivity, and (iii) transient expression in the apparent absence of both vesicular monoamine transporter 2 messenger RNA and tryptophan hydroxylase immunoreactivity. For example, hybridization for serotonin transporter messenger RNA was strong in serotonin cell body-containing areas beginning early in gestation, and remained intense through adulthood. Immunoreactivity for tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, was completely overlapping with the presence of serotonin transporter messenger RNA in raphe nuclei postnatally. Sensory relay systems including the ventrobasal nucleus (somatosensory), lateral and medial geniculate nuclei (visual and auditory, respectively) as well as trigeminal, cochlear and solitary nuclei were representative of the second class of observations. In general, the limbic system expressed serotonin transporter messenger RNA in the third pattern with various limbic structures differing in the timing of expression. Septum, olfactory areas and the developing hippocampus contained serotonin transporter messenger RNA early in the developing brain. Other regions such as cingulate and frontopolar cortex exhibited hybridization peri- and postnatally, respectively. Several hypothalamic nuclei and pituitary transiently expressed serotonin transporter messenger RNA either postnatally or perinatally, respectively. If the observed patterns correlate with functional protein expression, distinct classes of serotonin transporter messenger RNA expression may reflect different functional roles for the serotonin transporter and serotonin, itself. Since the serotonin transporter is a target for a number of addictive substances including cocaine and amphetamine derivatives as well as antidepressants, transient expression of the serotonin transporter might suggest a window of vulnerability of associated cells to fetal drug exposure. Re-uptake, storage and re-release from non-serotonergic neurons might serve as a feedback mechanism from target neurons to serotonergic neurons. Alternatively, the transient expression of serotonin transporter messenger RNA may reflect critical periods important for tight regulation of extracellular serotonin in several brain regions, and may indicate previously unappreciated roles for serotonin as a developmental cue.

Aging↗
PubMed1999

A brief history of psychiatry: millennia past and present--part II.

Institutional treatment of psychiatric disorders dates back at least to the time of Hippocrates, when there were efforts to improve patients' general health in pleasant surroundings. Institutions for the mentally ill and for abusers of addicting substances have varied through the centuries from squalid conditions to surroundings meant to improve psychological and social well being. In the eighteenth-century, Pinel, Rush, and others assumed that environmental changes could affect psychological states and alter behavior. Twentieth century debate has been concerned with whether or not patients are better treated in hospitals or in the community. Currently, the focus on minimizing health care costs has emphasized often-valuable intensive and not so intensive outpatient programs, almost to the exclusion of sometimes-necessary inpatient hospitalization. Contemporary social and political trends inside and outside the mental health professions include attempts to modify this emphasis and to focus on the specific needs of individual patients.

Antipsychotic Agents↗
PubMed1990

Alcohol myopia. Its prized and dangerous effects.

This article explains how alcohol makes social responses more extreme, enhances important self-evaluations, and relieves anxiety and depression, effects that underlie both the social destructiveness of alcohol and the reinforcing effects that make it an addictive substance. The theories are based on alcohol's impairment of perception and thought--the myopia it causes--rather than on the ability of alcohol's pharmacology to directly cause specific reactions or on expectations associated with alcohol's use. Three conclusions are offered (a) Alcohol makes social behaviors more extreme by blocking a form of response conflict. (b) The same process can inflate self-evaluations. (c) Alcohol myopia, in combination with distracting activity, can reliably reduce anxiety and depression in all drinkers by making it difficult to allocate attention to the thoughts that provoke these states. These theories are discussed in terms of their significance for the prevention and treatment of alcohol abuse.

Alcohol Drinking↗
PubMed2002

Do animal models provide a valid analogue for human drug lapse and relapse? Comment on Leri and Stewart (2002).

Prior research on animal models of drug relapse has demonstrated that passive exposure to an addictive substance following acquisition and extinction of drug self-administration has a "priming effect" on subsequent drug use. The validity of this animal analogue of human relapse can be criticized, however, because most human drug relapses are precipitated by the user's voluntary self-administration of a substance. The results of the present study by F. Leri and J. Stewart (2002) clearly show that if the initial heroin lapse is self-administered by rats, subsequent heroin seeking during the relapse test is significantly greater than if the heroin is externally administered. These results help bridge the gap between animal and human models of drug use and highlight the significance of both behavioral and environmental determinants of relapse.

Animals↗
PubMed1995

Suppression of psychoactive effects of cocaine by active immunization.

Cocaine is a powerfully addictive substance and new strategies are needed to treat its abuse. Generating an active immunization to cocaine offers a means of blocking the actions of the drug by preventing it from entering the central nervous system, and should have fewer side effects than treatments based on manipulation of central neurotransmitter function. The design and preparation of a cocaine immunogen requires special regard for the stability of cocaine both free and as a haptenic determinant. Immunochemistry and a well defined behavioural model were brought together to address the problem of inactivation of the psychostimulant actions of cocaine. We report here that active immunization with a new, stable cocaine conjugate suppressed locomotor activity and stereotyped behaviour in rats induced by cocaine but not by amphetamine. Moreover, following acute injection of cocaine, levels of cocaine in the striatum and cerebellum of the immunized animals were lower than those of control animals. These results suggest that immunopharmacotherapy may be a promising means by which to explore new treatments for cocaine abuse.

Animals↗
PubMed2004

Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving.

Using fMRI, our group previously found that after a sip of alcohol and exposure to alcohol beverage pictures, alcoholics compared to social drinkers had increased differential brain activity in the prefrontal cortex and anterior thalamus. This study extends this earlier work with several improvements including imaging the entire brain (rather than the anterior half previously) and recording craving, while the subjects viewed images within the scanner. In a Philips 1.5 T MRI scanner, 10 nontreatment-seeking alcoholics and 10 age-matched healthy social drinkers were given a sip of alcohol before viewing a 12 min randomized presentation of pictures of alcoholic beverages, nonalcoholic beverages, and two different visual control tasks. During picture presentation, changes in regional brain activity were measured in 15 transverse T2(*)-weighted blood oxygen level dependent slices. Subjects rated their urge to drink after each picture sequence. After a sip of alcohol, while viewing alcohol cues compared to viewing other beverage cues, the alcoholics, but not social drinkers, reported higher craving ratings and had increased activity in the prefrontal cortex and anterior limbic regions. Brain activity in the left nucleus accumbens, anterior cingulate, and left orbitofrontal cortex significantly correlated with subjective craving ratings in alcohol subjects but not in control subjects. This study suggests, as did our earlier study, that alcoholics and not social drinkers, when exposed to alcohol cues, have increased brain activity in areas that reportedly subserve craving for other addictive substances.

Adult↗
PubMed2006

Upregulation of ionotropic glutamate receptor subunits within specific mesocorticolimbic regions during chronic nicotine self-administration.

Nicotine, an addictive substance, is the major psychoactive component in cigarette smoke. Both alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate (NMDA) receptors are essential for the acute stimulative effects of nicotine on the mesocorticolimbic dopamine system, yet little is known about the effects of chronic nicotine treatment on glutamate receptors. Therefore, we used a model of chronic nicotine self-administration (SA), which emulates important aspects of nicotine intake by humans, to determine whether glutamate receptor subunits were affected. After 18 days of saline vs nicotine SA, ionotropic glutamate receptor subunit levels were determined in brain regions within the mesocorticolimbic system by Western blotting. In prefrontal cortex (PFC), the levels of NMDA receptor subunit 2A (NR2A) and NR2B were increased by 67% (p=0.04) and 83% (p=0.027), respectively. In the ventral tegmental area (VTA), glutamate receptor subunit 2/3 (GluR2/3) increased by 34% (p=0.011). Nicotine SA did not affect the expression of these subunits in dorsal striatum and nucleus accumbens. These findings suggest that chronic nicotine SA selectively increased the levels of ionotropic glutamate receptor subunits in a brain region-specific manner.

Animals↗
PubMed1997

Smoking among hospital doctors in Israel and their attitudes regarding anti-smoking legislation.

Anti-smoking legislation has been implemented in several countries. In order to study the attitudes of Israeli doctors to such legislation, 260 hospital doctors were questioned regarding their smoking habits and attitudes towards anti-smoking legislation. It was discovered that 15.8% are current smokers [40% of radiologists, 25% of surgeons and anesthetists, and 8% of internists and pediatricians (P = 0.0005)], of which 76% began smoking before the age of 20, and 54% tried to quit at least once. 24.2% of the current non-smokers are prior smokers who stopped, 92% of non-smokers and 83% of smokers tell their patients to quit (P = 0.10). 69% feel that cigarette sales should be limited to those of 18 y and older, 77% that advertisements for cigarettes should be prohibited, and 74% that nicotine should be recognized as an addictive substance. Doctors who smoke may have difficulty promoting healthy behavior among their patients. They must be offered help in order to quit, and emphasis should be placed on prevention among medical students.

Adult↗
PubMedDate not supplied

Relevance of frequent mu-opioid receptor polymorphisms for opioid activity in healthy volunteers.

Polymorphisms in the mu-opioid receptor gene (OPRM1) are primary candidate sources of clinical variability in opioid therapy. Apart from the 118A>G single nucleotide polymorphism, nothing is known about the role of OPRM1 mutations in opioid therapy. The influence of the OPRM1 mutations on opioid pharmacodynamics was assessed in pooled data from 31 healthy volunteers obtained in previous studies with available plasma concentrations and pupil diameters after intravenous administration of morphine or morphine-6-glucuronide (M6G). A total of 24 candidate ORPM1 mutations were screened for and those found at an allelic frequency of at least 5% in the 31 subjects were analyzed for functional consequences, using population pharmacokinetic-pharmacodynamic modeling of the miotic effects of the opioids as a reliable and sensitive surrogate parameter of the central nervous opioid effects. Polymorphisms at an allelic frequency of > or =5% (n=310) were 118A>G in exon 1 (11.5%), the IVS2-31G>A (8.9%) and IVS2-691C>G (44.5%) SNPs in intron 2. The 118A>G SNP significantly increased the values of EC50 by a factor of more than 2 (non-mutated: EC50,morphine=30 nmol/l, EC50,M6G=750 nmol/l, 118G carriers: EC50,morphine=66 nmol/l, EC50,M6G=1650 nmol/l), whereas the IVS2-691C>G SNP had no effect. Based on morphine and M6G, the present analysis encourages focusing on the 118A>G SNP when investigating the role of OPRM1 mutations for the activity of opioid analgesics. Other OPRM1 mutations are probably less important either owing to low allelic frequency or due to poor indications for functional consequences. This applies to opioid potency in the context of opioid therapy but not to pain processing or substance addiction, in which opioid receptors are involved but other or additional OPRM1 mutations may be important.

Alleles↗
PubMed2001

Delta9-tetrahydrocannabinol releases and facilitates the effects of endogenous enkephalins: reduction in morphine withdrawal syndrome without change in rewarding effect.

Recent studies have suggested that cannabinoids might initiate the consumption of other highly addictive substances, such as opiates. In this work, we show that acute administration of Delta9-tetrahydrocannabinol in mice facilitates the antinociceptive and antidepressant-like responses elicited by the endogenous enkephalins protected from their degradation by RB 101, a complete inhibitor of enkephalin catabolism. This emphasizes the existence of a physiological interaction between endogenous opioid and cannabinoid systems. Accordingly, Delta9-tetrahydrocannabinol increased the release of Met-enkephalin-like material in the nucleus accumbens of awake and freely moving rats measured by microdialysis. In addition, this cannabinoid agonist displaced the in vivo [3H]diprenorphine binding to opioid receptors in total mouse brain. The repetitive pretreatment during 3 weeks of Delta9-tetrahydrocannabinol in mice treated chronically with morphine significantly reduces the naloxone-induced withdrawal syndrome. However, this repetitive administration of Delta9-tetrahydrocannabinol did not modify or even decrease the rewarding responses produced by morphine in the place preference paradigm. Taken together, these behavioural and biochemical results demonstrate the existence of a direct link between endogenous opioid and cannabinoid systems. However, chronic use of high doses of cannabinoids does not seem to potentiate the psychic dependence to opioids.

Analgesics↗
PubMed1999

Comparison of primary care resident physicians' practice styles during initial and return patient visits.

New adult patients (n = 212) were randomly assigned to 58 primary care resident physicians. Physician practice styles during initial and return visits were analyzed using the Davis Observation Code. Compared with initial patient visits, return visits were shorter, but more work-intensive. Return visits displayed significantly less technically oriented behavior (including history taking, physical examination, and treatment planning) and fewer discussions regarding use of addictive substances; however, there was more emphasis on health behaviors and active involvement of patients in their own care. These physicians' practice style differences between initial and return patient visits suggest that physician-patient familiarity affects what happens during the medical interview.

Adult↗
PubMed2003

[Single or Mixed Sex Wards in Psychiatric Hospital from the Patients' Viewpoint]

OBJECTIVE: Preference on separate or mixed sex treatment should be evaluated from the viewpoint of patients of a psychiatric hospital. METHODS: The preference of patients were surveyed by questionnaire before and after mixing four single sex wards. The adjusted response rate was 74.5 %. RESULTS: About 75 % of psychiatric patients prefer a mixed sex ward, about 25 % prefer a single sex ward. Females more frequently confirm the type of ward to whom they were actually allocated. By contrast, males are in favour for mixed sex wards independently of the presently experienced type of ward. Younger patients, voluntarily admitted patients, and patients with substance addiction prefer mixed sex wards. After mixing the sexes of formerly single sex wards a significant increase in preference of mixed sex wards was found, due to increased affirmation by female patients. CONCLUSION: If single sex wards can be established in a psychiatric hospital considering their size, specialisation of wards, and sector of care, patients are enabled to choose between a single and mixed sex ward at admission.

Journal Article↗
PubMed2004

A single cocaine exposure enhances both opioid reward and aversion through a ventral tegmental area-dependent mechanism.

Repeated exposure to drugs of abuse produces forms of experience-dependent plasticity including behavioral sensitization. Although a single exposure to many addicting substances elicits locomotor sensitization, there is little information regarding the motivational effects of such single exposures. This study demonstrates that a single cocaine exposure enhances both rewarding and aversive forms of opioid place conditioning. Rats were given a single injection of cocaine (15 mg/kg i.p.) in their home cage at different times before conditioning. This treatment enhanced conditioned place preference (CPP) to morphine (2 x 10 mg/kg s.c.) if training began 1 or 5 but not 10 days after the cocaine injection. A single cocaine exposure also enhanced conditioned place aversion (CPA) to the kappa-opioid receptor agonist U69593 (2 x 0.16 mg/kg s.c.). Compared to morphine CPP, U69593 CPA was delayed and persistent. It was not observed at 1 day but appeared if the conditioning began 5 or 10 days after the cocaine injection. Although the cocaine-induced enhancements of both morphine CPP and U69593 CPA followed different time courses, suggesting different mechanisms, both effects were blocked by injection of the N-methyl-d-aspartate receptor antagonist MK-801 (0.5 nmol bilaterally) into the ventral tegmental area, immediately before the cocaine injection. Thus, through a circuit involving the ventral tegmental area, a single cocaine exposure enhanced both micro-opioid receptor reward and kappa-opioid receptor aversion.

Analgesics, Opioid↗
PubMed2003

Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence.

In addition to their physiological function, metabotropic receptors for neurotransmitter gamma-aminobutyric acid (GABA), the GABA(B) receptors, may play a role in the behavioral actions of addictive compounds. Recently, GABA(B) receptors were cloned in fruit flies (Drosophila melanogaster), indicating that the advantages of this experimental model could be applied to GABA(B) receptor research. RNA interference (RNAi) is an endogenous process triggered by double-stranded RNA and is being used as a tool for functional gene silencing and functional genomics. Here we show how cell-nonautonomous RNAi can be induced in adult fruit flies to silence a subtype of GABA(B) receptors, GABA(B)R1, and how RNAi combined with pharmacobehavioral techniques (including intraabdominal injections of active compounds and a computer-assisted quantification of behavior) can be used to functionally characterize these receptors. We observed that injection of double-stranded RNA complementary to GABA(B)R1 into adult Drosophila selectively destroys GABA(B)R1 mRNA and attenuates the behavioral actions of the GABA(B) agonist, 3-aminopropyl-(methyl)phosphinic acid. Moreover, both GABA(B)R1 RNAi and the GABA(B) antagonist CGP 54626 reduced the behavior-impairing effects of ethanol, suggesting a putative role for the Drosophila GABA(B) receptors in alcohol's mechanism of action. The Drosophila model we have developed can be used for further in vivo functional characterization of GABA(B) receptor subunits and their involvement in the molecular and systemic actions of addictive substances.

Animals↗
PubMed2001

Parasuicides without follow-up.

The aim of this project was to approach subjects who committed parasuicide but did not primarily receive or accept a recommendation for care through the regular routines after referral to a general hospital. Three hundred and twenty-nine consecutive parasuicides in 10- to 89-year-olds (162 men and 167 women) were studied. One hundred were subsequently hospitalized in the departments of psychiatry, 130 were followed up at outpatient facilities, and 96 left without any follow-up. A psychiatric liaison consultation was made in 57% of the total sample. The 96 subjects without follow-up were compared with the subjects who received follow-up. The sample was somewhat younger and included slightly more men. They were single in 54% and unemployed in 43% of the cases. According to the DSM-IV, 27% had a concurrent depression. According to the CAGE questions, 57% had indication of substance addiction. Fifty-four per cent had currently low global functioning, less than 50 points on the GAF. They had not been in contact with psychiatric care previously to the same extent as the others. About 34% of these who did not receive or rejected follow-up initially after a second approach agreed to follow-up when contacted by the project team, referring them to appropriate authorities such as social welfare offices, family counselling, or psychosocial staff within psychiatry or primary care. This may imply that the group delineated is at risk for eventual suicide and that the acceptance of follow-up should be interpreted as an indication that a substantial number needs help and can be successfully encountered by means of a case manager approach.

Adolescent↗
PubMed2006

Comparative cost-effectiveness of policy instruments for reducing the global burden of alcohol, tobacco and illicit drug use.

Alcohol, tobacco and illicit drug use together pose a formidable challenge to international public health. Building on earlier estimates of the demonstrated burden of alcohol, tobacco and illicit drug use at the global level, this review aims to consider the comparative cost-effectiveness of evidence-based interventions for reducing the global burden of disease from these three risk factors. Although the number of published cost-effectiveness studies in the addictions field is now extensive (reviewed briefly here) there are a series of practical problems in using them for sector-wide decision making, including methodological heterogeneity, differences in analytical reference point and the specificity of findings to a particular context. In response to these limitations, a more generalised form of cost-effectiveness analysis (CEA) is proposed, which enables like-with-like comparisons of the relative efficiency of preventive or individual-based strategies to be made, not only within but also across diseases or their risk factors. The application of generalised CEA to a range of personal and non-personal interventions for reducing the burden of addictive substances is described. While such a development avoids many of the obstacles that have plagued earlier attempts and in so doing opens up new opportunities to address important policy questions, there remain a number of caveats to population-level analysis of this kind, particularly when conducted at the global level. These issues are the subject of the final section of this review.

Alcohol Drinking↗
PubMed2000

Policy interventions to reduce the harm from smoking.

The other papers in this series on reduced smoking discuss interventions focused on individuals. This paper illustrates possible smoking reduction interventions focused on policies rather than individuals. Target 12 of the new WHO Health For All Policy aims to significantly reduce the harm from addictive substances, including tobacco, in all member states by 2015, and the WHO Third Action Plan for Tobacco-Free Europe focuses on reducing the harm from tobacco. These documents recommend five key policy strategies: market regulation, product liability, smoke-free environments, support for smoking cessation and education, public information and public opinion. Interventions such as price increases, restricting availability, advertising bans and product control could all be used to achieve harm reduction. Research on reducing the harm of smoking needs to include policy as well as treatment research.

Advertising↗