Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance. We recently established a mouse model of heroin addiction in which, following chronic heroin exposure, 'abstinent' mice progressively develop a strong and long-lasting social avoidance phenotype. Here, we explored and compared the efficacy of two pharmacological interventions in this mouse model. Because clinical studies indicate some efficacy of antidepressants on emotional dysfunction associated with addiction, we first used a chronic 4-week treatment with the serotonergic antidepressant fluoxetine, as a reference. In addition, considering prodepressant effects recently associated with kappa opioid receptor signaling, we also investigated the kappa opioid receptor antagonist norbinaltorphimine (norBNI). Finally, we assessed whether fluoxetine and norBNI could reverse abstinence-induced social avoidance after it has established. Altogether, our results show that two interspaced norBNI administrations are sufficient both to prevent and to reverse social impairment in heroin abstinent animals. Therefore, kappa opioid receptor antagonism may represent a useful approach to alleviate social dysfunction in addicted individuals.

Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains.

RATIONALE: Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure. OBJECTIVES: While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds. METHODS: Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period. RESULTS: Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J. CONCLUSIONS: Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.

Kinetic analysis of the loss of some B-vitamins during the cooking of macaroni.

The kinetics of the losses of thiamin, niacinamide, and riboflavin were investigated during the cooking of macaroni at 50, 75, 80, 85, and 90 degrees C. Simultaneous analysis of the vitamins was achieved by HPLC using a mu-Bondapak column. The activation energies for the losses of thiamin, niacinamide, and riboflavin were determined as 25 kJ/mol, 22 kJ/mol, and 11 kJ/mol, respectively. It was concluded that the leaching of these vitamins into cooking water was the main pathway for their loss during macaroni preparation.

Transient-phase and steady-state kinetics of lipase-catalyzed ester hydrolysis.

An experimental study has been made of both the steady-state and the transient-phase (presteady-state) kinetics of the hydrolyses of several saturated aliphatic esters of p-nitrophenol catalyzed by wheat germ lipase. The analysis of the presteady- 1 Presented in part at the 173rd ACS National Meeting, New Orleans, L.A., U.S.A., March 20--25, 1977. 2 Correspondence should be addressed to M.H. Sadar, E.S.D., E.H.C., Health and Welfare Canada, Tunney's Pasture, Ottawa, Ontario, Canada, K1A OL2. 3 Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada. state part revealed two transients indicating that lipase-catalyzed reactions proceed via a two-intermediate mechanism suggested for other esterases. The possibility of more than one species of the enzyme engaged in catalytic activity is discussed and a reaction mechanism scheme is proposed accordingly.