argipressin--des-glynh2(9)- and Alcoholism

Among the many factors that may influence the development or expression of functional tolerance to or physical dependence on ethanol is the neurohypophyseal hormone, arginine vasopressin (AVP). This peptide hormone, administered exogenously, maintains ethanol tolerance in animals once such tolerance has been established. An analog of the hormone has also been reported to facilitate the development of ethanol tolerance and to exacerbate ethanol withdrawal symptomatology. Neurohypophyseal hormones and structurally related peptides have previously been shown to influence learning or memory; however, structure-activity analyses reveal differences in the structural requirements for maintenance of ethanol tolerance as compared to facilitation of memory processes. Therefore, these phenomena may represent CNS adaptive processes which are subserved by different mechanisms, or are differentially sensitive to particular peptides. The initial sensitivity of an animal to ethanol can also be affected by peptides, notably thyrotropin releasing hormone (thyroliberin, TRH). TRH antagonizes many of the initial responses to ethanol, perhaps by non-specific means. AVP, however, appears to potentiate the sedative effect of an acute dose of ethanol. Neurohypophyseal peptides also modulate ethanol intake. Thus, these neuropeptides, which have been localized to many areas of brain, may serve as endogenous modulators of various parameters related to ethanol consumption.

Topics: Adrenocorticotropic Hormone; Alcohol Drinking; Alcoholism; Animals; Arginine Vasopressin; Brain; Drug Tolerance; Ethanol; Humans; Hydroxydopamines; Lypressin; Male; Mice; Mice, Inbred C57BL; Neurotransmitter Agents; Oxidopamine; Oxytocin; Pituitary Hormones; Rats; Thyrotropin-Releasing Hormone

The effect of intranasally administered (DesGly9-Arg8) vasopressin (DGAVP) on certain aspects of cognitive functions of alcoholic patients was studied. The investigation was carried out in 103 chronic alcoholic patients. None of the patients suffered from Korsakoff's syndrome, portal encephalopathy or brain damage of other etiology. The trial was double-blind, placebo controlled. Psychological testing, which included certain aspects of attention, short-term and long-term memory and spatial orientation, was carried out on the day before (baseline measurements), on the last day (II), and seven days after the last administration of DGAVP (III). No treatment effect of DGAVP was observed. The results show that investigations with humans are infinitely more complex than those with animals, since a number of physiological and socio-psychological factors must be controlled. In this study of alcoholics two such factors: 1) duration of abstinence and 2) adaptation to test situation were identified.

Topics: Adult; Alcoholism; Arginine Vasopressin; Cognition; Humans; Male; Middle Aged; Temperance

Intranasal treatment with desglycinamide9-(Arg8)-vasopressin (DGAVP) improved certain aspects of cognitive functions of patients with acquired and congenital diabetes insipidus and of alcoholic patients with mild cognitive impairments. Patients with Korsakoff's syndrome, presenting with severe cognitive impairments, were resistent to DGVP treatment. DGAVP treatment did not affect blood pressure and water metabolism. The action of DGAVP on cognitive functions is probably mediated by centrally located target sites and may be expressed only in patients in whom these target sites are unimpaired.

Topics: Administration, Intranasal; Adult; Aged; Alcohol Amnestic Disorder; Alcoholism; Arginine Vasopressin; Clinical Trials as Topic; Cognition; Diabetes Insipidus; Double-Blind Method; Female; Humans; Male; Middle Aged; Psychological Tests

Vasopressin peptides have been shown to facilitate learning and memory in both animals and humans; however, the effectiveness in humans is controversial. In a double blind parallel group study, 17 demented subjects (either Alzheimer's or alcoholic) were given either desglycinamide-9-arginine-8-vasopressin (DGAVP) 92 micrograms intranasally TID or an identical placebo for 1 week after having received 1 week of placebo. To our knowledge, this is the first report of DGAVP being used in subjects with dementia. The DGAVP group had a statistically significant improvement on the Buschke list learning of low imagery words. However, for various reasons discussed in the paper, we feel this finding needs to be replicated before any definite conclusions can be drawn. Since there were no other appreciable behavioral effects of this DGAVP regimen, our results should be considered negative. There was no evidence of any DGAVP-related adverse effects, except for possible weight gain.

Topics: Affect; Aged; Alcoholism; Alzheimer Disease; Arginine Vasopressin; Clinical Trials as Topic; Dementia; Humans; Learning; Mental Recall; Middle Aged

Evidence is accumulating that hormonal systems present in the pituitary and the brain play a critical role in behavioral homeostase. The hormones and their fragments, called neuropeptides, produced by these systems modulate neurotransmitter activity and thereby control brain functions. Disturbances in this hormonal control may result in psychopathology, including addiction. Vasopressin and related peptides decrease under certain conditions addictive behavior of experimental animals and humans and brain reward. The pituitary and brain opioid peptides are candidates to play an essential role in reward processes and may be common factors in addiction to various psychoactive drugs, including heroin and alcohol, and to habits. Other pituitary hormones, like ACTH, gamma 2-MSH and prolactin have also been implicated in brain reward and drug addiction. It is postulated that disturbances in the hormonal and neuropeptide systems may lead to a state in which addiction behavior can easily be elicited and that the hormonal climate in the body may be of relevance for the individual susceptibility to addictive drugs. It is proposed to analyse the relation between hormonal systems and addictive behavior.

Topics: Adrenocorticotropic Hormone; Alcoholism; Animals; Arginine Vasopressin; beta-Endorphin; Brain; Endorphins; Haplorhini; Heroin Dependence; Humans; Melanocyte-Stimulating Hormones; Naltrexone; Neurotransmitter Agents; Peptides; Pituitary Gland; Rats; Reinforcement, Psychology; Reward; Substance-Related Disorders

Rats trained to walk in a moving belt apparatus were subjected to a partial (fornix-fimbria (FF] or total (fornix-fimbria + cingulum bundles (FF + CB] chemical denervation of the dorsal serotonergic afferent pathways to the hippocampus. After chronic alcohol treatment that resulted in tolerance development to the motor-impairing effects of ethanol, desglycinamide-arginine8-vasopressin (DGAVP) or saline treatment was started and the residual tolerance measured at several intervals after ethanol withdrawal. DGAVP administration resulted in a virtually complete retention of ethanol tolerance when given to sham-operated controls or FF-lesioned rats. The peptide treatment failed, however, to prolong tolerance in rats bearing a complete FF + CB lesion, that reduced serotonin (5-HT) levels in the hippocampus and overlying parietal cortex to 10 and 45% of controls respectively. These results suggest that the serotonergic innervation of these areas is necessary for the action of DGAVP in the maintenance of ethanol tolerance.

Topics: Alcoholism; Animals; Arginine Vasopressin; Brain Mapping; Drug Interactions; Drug Tolerance; Ethanol; Hippocampus; Humans; Male; Rats; Rats, Inbred Strains; Serotonin