argipressin--des-glynh2(9)- and Substance-Related-Disorders

The effect of the vasopressin neuropeptide desglycinamide9, (Arg8) vasopressin (DGAVP) on the acquisition of intravenous cocaine self-administration was studied. Rats were tested under conditions of reduced body weight in a continuous reinforcement operant procedure, during five daily 3 h sessions. Under these conditions, the rate of self-administration obtained with 0.125 and 0.25, but not 0.063 mg.ml-1 cocaine, exceeded the rate obtained with saline. Daily pretreatment with DGAVP (5 micrograms/rat, s.c.) decreased self-administration of 0.125 and 0.25 mg.ml-1 cocaine to the level obtained with saline, but had no effect on self-administration of 0.063 mg.ml-1 cocaine and saline. Using a similar procedure, it was shown that daily intracerebroventricular pretreatment with vasopressin antiserum significantly increased self-administration of 0.125 mg.ml-1 cocaine, without affecting self-administration of 0.063 and 0.25 mg.ml-1 cocaine and saline. The results support previous findings obtained with vasopressin neuropeptides in drug self-administration studies and suggest that DGAVP decreases the acquisition of cocaine self-administration by attenuating the reinforcing effects of cocaine and that endogenous vasopressin may be involved in the acquisition of cocaine self-administration.

Topics: Animals; Antigen-Antibody Reactions; Arginine Vasopressin; Cocaine; Immunologic Techniques; Male; Rats; Self Administration; Substance-Related Disorders; Vasopressins

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

Mice were rendered physically dependent on ethanol by inhalation of ethanol vapour and treatment with pyrazole for 3 days. On Day 4, withdrawal convulsions were measured and on Day 5 or later, residual tolerance to the hypothermic effect of an i.p. challenge dose of 3 g/kg ethanol was assessed. Mice continuously infused with the vasopressin fragment des-Gly9-[Arg8]-vasopressin dicitrate (DGAVP) throughout the periods of dependence induction and withdrawal testing exhibited exacerbated withdrawal convulsions. DGAVP also tended to exacerbate withdrawal when injected s.c. repeatedly (10 micrograms/injection/mouse) during testing for withdrawal. The data indicate that these effects were not likely to have been due to subconvulsive activity of DGAVP by itself or to changes in blood levels of ethanol. Continuous infusion of DGAVP enhanced residual tolerance on Day 5 but did not maintain tolerance when the time interval between withdrawal and testing for tolerance was increased. Restricting treatment with DGAVP to the period of induction of dependence (Days 1-3) also enhanced tolerance on Day 5. The data indicate that the vasopressin fragment modulates the development and/or the decay of tolerance to ethanol. In addition it exacerbates withdrawal convulsions, an effect that may be due to modulation of physical dependence.

Topics: Animals; Arginine Vasopressin; Drug Tolerance; Ethanol; Humans; Mice; Pentylenetetrazole; Pyrazoles; Substance Withdrawal Syndrome; Substance-Related Disorders