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A Bisaga

Publications and source records attributed to A Bisaga.

15 recordsLinked to original sources
PubMed2003

Effects of memantine, an NMDA receptor antagonist, on place preference conditioned with drug and nondrug reinforcers in mice.

Antagonists of the N-methyl-D-aspartate (NMDA) receptor complex have been shown to inhibit the expression of place preferences conditioned with several drugs that are abused by humans, which suggests that this class of compounds may be beneficial in the treatment of substance dependence. Therefore it is important to assess the specificity of this effect, of whether inhibitory effects of NMDA receptor antagonists on conditioned drug stimuli generalize to behaviors produced by nondrug reinforcers. The present study was designed to compare the effects of the NMDA receptor channel blocker, memantine, on the expression of place preferences conditioned with: (1) consumption of regular laboratory food; (2) sexual encounters with females; and (3) injection of morphine (10 mg/kg) in adult male Swiss mice. For all three experiments reported here, unconditioned stimuli (food, receptive female or morphine) were presented before the exposures to the "to-be-conditioned" environments. Significant place preferences developed as a result of explicit pairings of the environmental context and food consumption, sexual encounter and morphine administration. Memantine (7.5 mg/kg, given prior to the post-conditioning test) inhibited the expression of place preferences conditioned with morphine and sexual encounter, but had no effects in food-conditioned mice. These findings suggest that the effects of NMDA receptor blockade may not be limited to drug-reinforced behaviors.

Animals↗
PubMed2001

The NMDA antagonist memantine attenuates the expression of opioid physical dependence in humans.

RATIONALE: Preclinical observations suggest that NMDA receptor-mediated glutamatergic neurotransmission is involved in the expression and maintenance of opioid dependence. OBJECTIVE: The present study evaluated whether memantine, the clinically available non-competitive NMDA receptor antagonist, decreases naloxone-precipitated withdrawal in morphine-dependent humans. METHODS: Eight heroin-dependent, non-treatment seeking, inpatient participants were stabilized on a fixed dose of morphine (30 mg PO qid). Subsequently, they received a series of challenges with naloxone (0.4 mg, IM) and the severity of opioid withdrawal was monitored. Either placebo or memantine (60 mg PO) was given 6 h before each naloxone challenge. A modified multiple baseline, across-participants design was used to evaluate the effects of memantine on the severity of naloxone-precipitated opioid withdrawal. RESULTS: Naloxone increased ratings and produced physical changes consistent with opioid withdrawal. Memantine attenuated the severity of opioid withdrawal as assessed with the Clinical Institute for Narcotic Withdrawal Scale scale. Withdrawal was significantly reduced when naloxone was administered at 6 and 52 h after memantine, but not when administered 126 h (5 days) after memantine. Medication effects, assessed 5 h after memantine administration and before naloxone administration, included significant increases in ratings of "strong" and "good" drug effect, and "I feel sedated", "mellow", and "high". CONCLUSIONS: Memantine attenuated the expression of opioid physical dependence in humans, indicating that glutamatergic neurotransmission at the NMDA receptor site contributes to the maintenance of opioid dependence. This finding suggests that memantine may be a useful adjunct in the treatment of opioid dependence.

Adult↗
PubMed2000

In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-D-aspartate (NMDA) antagonists.

The most challenging aspect of treating alcohol and drug addiction is the relapsing course of these disorders. Although substitution therapies for nicotine and opioid dependence have proven to be relatively effective, there is a need for new pharmacotherapies designed to decrease the frequency and severity of relapse. The aim of this paper is to provide an overview of the potential utility of N-methyl-D-aspartate (NMDA) receptor antagonists as treatments for substance abuse as shown in preclinical models and preliminary clinical trials. It is hypothesized that NMDA receptors mediate the common adaptive processes that are involved the development, maintenance, and expression of drug and alcohol addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists offers a novel treatment approach. It is proposed that NMDA antagonists may have multiple functions in treating addictions, including an attenuation of withdrawal effects, normalization of the affective changes following initiation of abstinence which arise from neurochemical changes resulting from chronic addiction, and an attenuation of conditioned responses arising from drug-related stimuli.

Alcoholism↗
PubMed2000

Therapeutic potential of NMDA receptor antagonists in the treatment of alcohol and substance use disorders.

Despite the fact that the use of alcohol, nicotine and other drugs is the major external factor contributing to mortality in industrialised countries, there are few medications available to treat alcohol and substance use disorders. In recent years, major advances have been made in the understanding of the neurobiological basis for these disorders and these advances should lead to the development of new pharmacotherapeutics. A substantial amount of the research suggests that N-methyl-D-aspartate (NMDA) receptor neurotransmission contributes to mediating the behavioural effects of alcohol and other drugs of abuse. This research supports the therapeutic potential of NMDA receptor antagonists in alcohol and substance use disorders. In this paper the authors present their opinion on the goals and stages of pharmacological treatment of these complex psychiatric disorders. Available preclinical research using designs that model aspects of alcohol and substance use disorders is summarised, with an emphasis on research published in the last two years. In animal models, NMDA antagonists inhibit physical dependence and the reinforcing effects of a variety of abused substances. The ability of NMDA antagonists to inhibit tolerance to drug effects and contribute possible antidepressant and anxiolytic effects are also important from the perspective of drug development. This review summarises the relevant clinical laboratory and treatment data. Finally, it presents the status of the current development of NMDA receptor antagonists and discusses candidates with the greatest potential for clinical development.

Alcoholism↗
PubMed2000

[Contemporary methods in pharmacotherapy in the opiate dependent treatment].

In this review, we present methods of pharmacotherapy in opiate dependence currently used in Poland and worldwide. As problems associated with drug abuse increase in severity, it is particularly important to bring these methods to the attention of medical professionals, governmental agencies and the general public. Here we describe pharmacotherapeutic approaches used in detoxification as well as relapse prevention. The presented methods of detoxification include classical treatments with clonidine and methadone as well as newer methods of rapid and ultrarapid detoxification. Agonists, partial agonists, and antagonists can be used in preventing relapse in detoxified patients. Experimental therapeutic approaches in the treatment of drug dependence are also presented. Psychotherapy and psychiatric care, central to the successful treatment of opiate dependence, are reviewed as well.

Adrenergic alpha-Agonists↗
PubMed1998

Cerebral glucose metabolism in women with panic disorder.

OBJECTIVE: This study was undertaken to clarify earlier inconsistent findings in brain metabolic topography in panic disorder patients at rest. METHOD: Positron emission tomography (PET) with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in six female patients with a DSM-III-R diagnosis of panic disorder and in six healthy female volunteers. All patients with panic disorder were medication free and were sensitive to lactate infusion. RESULTS: A significant increase in glucose metabolism was found in the left hippocampus and parahippocampal area of the panic disorder subjects in comparison with that found in the healthy subjects. In addition, a significant decrease in metabolism was found in the right inferior parietal and right superior temporal brain regions of the panic disorder subjects in comparison with that of the normal subjects. There was no significant correlation between scores for the severity of panic disorder or for the severity of lactate-induced panic attack and the quantified PET abnormality. CONCLUSIONS: These data provide further support for the hypothesis of an abnormal brain metabolism in the hippocampal and parahippocampal area in individuals with panic disorder and also suggest other areas of aberrant brain metabolism in this disorder.

Adult↗
PubMed1993

Effect of glutamate receptor antagonists on N-methyl-D-aspartate- and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced convulsant effects in mice and rats.

Selected antagonists of N-methyl-D-aspartate (NMDA) and (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists, acting through different recognition sites were studied in three in vivo experimental procedures: systemic administration of NMDA or AMPA to mice and 7-day-old rats or i.c.v. injection in adult rats. Antagonists were given i.p. before the agonists. Of the substances tested (+)-5-methyl-10,11- dihydro-5H-dibenzocyclohepten-5,10-imine maleate ((+)-MK-801, an uncompetitive NMDA receptor antagonist) and DL-(E)-2-amino-4-methyl-5- phosphono-3-pentanoic acid (CGP-37849, a competitive NMDA receptor antagonist) were the most potent and selective NMDA receptor antagonists, having ED50s below 1 mg/kg in all three tests. 1-Amino-3,5-dimethyladamantane (memantine, an uncompetitive NMDA receptor antagonist) was less potent and, additionally, inhibited AMPA-induced seizures in adult rats. Aminocyclopropane carboxylic acid--a partial agonist at the glycine site coupled to NMDA receptors (GlyB)--was a weak antagonist (ED50 > 150 mg/kg) in mice. Other partial GlyB receptor agonists, aminocyclobutane carboxylic acid, (+,R)-3-amino-1-hydroxy-2-pyrrolidine ((+,R)-HA-966) and d-cycloserine, and antagonists, 5,7-dinitroquinoxaline-2,3-dione (MNQX) and 5,7-dichlorokynurenic acid, were ineffective in mice after systemic administration. The last two agents however were active in adult rats when given i.c.v. Thus affinity, intrinsic activity (GlyB receptor partial agonists) and/or penetration into the brain (GlyB receptor antagonists) seem to be important factors in determining the effectiveness of these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Individual behavioral differences and ethanol consumption in Wistar rats.

The aim of this study was to determine if inherent differences in the behavioral measures between individual Wistar male rats influence the level of ethanol consumption. We addressed this question by searching for differences in ethanol intake that an individual animal develops. Measures of ethanol intake were then correlated with the outcome of various behavioral tests. Our results indicate that individual variations of behavioral reactivity may be associated with the predisposition to develop high ethanol intake. Animals with delayed habituation to a novel environment, enhanced locomotor activity during testing in the open field after initial habituation, and excessive locomotor inhibition after administration of 0.07 mg/kg dose of apomorphine, are predisposed to develop high ethanol intake in a free-choice condition. Measures of activity in the forced swim test, apomorphine-induced stereotypy, hypothermia, and locomotor stimulation could not predict a propensity to acquire high ethanol preference. It is suggested that individual differences in the acquisition of high ethanol intake may be influenced, at least partially, by the differences in the sensitivity of brain dopaminergic neurotransmission.

Alcohol Drinking↗
PubMedDate not supplied

Recognition cue in the rat's social memory paradigm.

The cue used by an adult resident rat for recognition of a just met juvenile in the social memory paradigm was assessed by manipulating the amount of olfactory information and enhancing the recognition with arginine8-vasopressin (AVP). Social recognition was impaired in anosmic resident rats, suggesting that the recognition cue is olfactory in nature. Washed juveniles were recognized by AVP but not placebo treated residents, independently of whether after washing they were marked with previously collected urine of the residents or not. Preputialectomized juveniles were recognized neither by placebo nor by AVP treated residents. The results suggest that the scents originating from the preputial gland of the juvenile serve as the recognition cue in the social memory paradigm of rats.

Animals↗
PubMedDate not supplied

[Selected issues of biological aspects of eating disorders].

This paper reviews the recent progress in the understanding of the neurobiology of the eating disorders. The analysis of the biochemical abnormalities present in the patients with bulimia nervosa indicates the decrease of central serotonin and noradrenalin activity, elevation of the levels of cerebrospinal fluid peptide YY, alterations of the endogenous opioids and also reduction of peripheral cholecystokinin levels. As these studies were performed on patients who were actively binging and purging it is conceivable that the above abnormalities can results from a pathological feeding pattern. It is also suggested that the reduction of central serotoninergic activity is the stable, trait-related dysregulation of neurotransmitter system activity. In patients with anorexia nervosa the endocrine disturbances of the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axes were thoroughly studied. Underweight anorectic patients have been found to have elevations of cerebrospinal fluid level of neuropeptide Y, corticotropin releasing hormone and vasopressin as well as reductions of beta-endorphin and oxytocin level. However, most of the neuropeptide alterations normalize following weight recovery. The only exception is a persistent increase of central serotonin activity postulated to be responsible for the obsessive-compulsive personality traits and disturbed eating behaviors found in these patients.

Anorexia Nervosa↗
PubMedDate not supplied

Studies on the effects of certain 5-HT-3 receptor antagonists on ethanol preference and withdrawal seizures in the rat.

We tested how certain antagonists of 5-HT-3 receptors affect ethanol consumption and withdrawal seizures in ethanol-dependent Wistar male rats. Low doses of tropisetron (0.001-0.01 mg/kg ip) and ondansetron (0.00025 mg/kg ip) reduced ethanol consumption and preference. Increased ethanol intake was observed, however, after administration of higher doses of ondansetron (0.125 g/kg ip) and granisetron (0.125-0.25 mg/kg ip). Audiogenic seizures in rats withdrawn from ethanol were attenuated by low doses of tropisetron and ondansetron.

Acoustic Stimulation↗
PubMedDate not supplied

The effect of drugs interacting with serotonergic 5HT3 and 5HT4 receptors on morphine place conditioning.

The effect of 5HT3 and 5HT4 active compounds on the motivational properties of morphine has been examined in the place conditioning (PC) paradigm using unbiased procedure. Place conditioning with morphine produced significant place preference. Pretreatment with the DAU 6285 (mixed 5HT3 antagonist--5HT4 antagonist) abolished morphine-induced PC. Ondansetron (selective 5HT3 antagonist) attenuated morphine place preference at the dose of 0.1 mg/kg. BIMU 8 (mixed 5HT3 antagonist--5HT4 agonist) failed to modify morphine PC in the 0.001-0.1 mg/kg dose range. While ondansetron given alone failed to produce place conditioning, pairing of BIMU 8 (0.001 mg/kg) induced significant place preference. On the other hand, animals were frequently avoiding compartment paired with the injection of DAU 6285. These findings suggest that 5-hydroxytryptamine by means of 5HT4 receptors mediates appetitive properties of morphine induced-stimuli and suggest that 5HT4 receptor may be involved in the brain reward and reinforcement processes.

Animals↗
PubMedDate not supplied

Selective breeding of rats differing in voluntary ethanol consumption.

Selective breeding of Wistar rats for the voluntary ethanol consumption is being carried out. Five generations have been achieved of ethanol high preferring and ethanol low preferring lines. Significant segregation between lines has been accomplished. In general, the results obtained replicate the previous findings with the genetic selection for voluntary ethanol consumption with the exception of poor results of downward selection.

Alcohol Drinking↗
PubMedDate not supplied

Effects of 5-HT3 receptor antagonists on ethanol-induced hyperlocomotion in mice.

We tested how 5-HT3 receptor antagonists, tropisetron (TR) and ondansetron (ON) affect the hyperlocomotion induced by single dose of ethanol EtOH) in mice. EtOH in a dose-dependent manner (0.5-2.0 g/kg ip) increased locomotion of mice. The effect of 2.0 g/kg of EtOH was reduced by ON (0.1 mg/kg and 1.0 mg/kg sc) and, to the lesser extent and only in limited dose range (0.01 mg/kg) by TR. Tropisetron (but not ON) increased concentrations of EtOH in the blood. The data suggest that 5-HT3 receptor is involved in EtOH-induced hyperlocomotion.

Animals↗