Alcohol is far more frequently associated with violent and aggressive behavior than all other drugs combined. The proposed research addresses our need to better understand the basic behavioral and neurobiological mechanisms of the alcohol-aggression link. Based on the discovery in the previous funding period that it is possible in several animal models to identify those individuals that are most prone to the aggression- heightening effects, the current proposal aims to delineate the behavioral, physiological and neurochemical characteristics of this subgroup of individuals. The marked individual differences in the aggression-heightening effects of alcohol and in the self-administration pattern for alcohol prompt focus on individual behavioral and physiological characteristics. Detailed investigations of GABA/A receptors using both pharmacological and endocrinological manipulations will examine this critical site of alcohol action in the modulation of aggressive behavior and related emotional expressions. Six series of experiments are proposed, the first focusing on the reciprocal relationship between aggression, social stress and alcohol self- administration, the second on a quantitative ethological analysis of the disruption of communicative social signals by alcohol and their neural modulation at GABA/A receptors, the third and fourth on the pharmacological and endocrinological influences on the benzodiazepine/GABA/A receptor complex for attenuating the aggression- heightening effects of alcohol, and the fifth and sixth on the behavioral, physiological and neurochemical characteristics of those individuals who are most prone to show aggression-heightening effects of alcohol. (1) Quantitative analysis of circadian rhythmicity of telemetered blood pressure, heart rate and core temperature, (2) autonomic response and adaptation to environmental, social and pharmacological challenges and (3) functional properties of GABA/A receptor populations are investigated for their predictive values to identify individuals with high propensity to become very aggressive after alcohol.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AA005122-13
Application #
2043083
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1993-01-01
Project End
1996-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Tufts University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
Miczek, Klaus A; Nikulina, Ella M; Takahashi, Aki et al. (2011) Gene expression in aminergic and peptidergic cells during aggression and defeat: relevance to violence, depression and drug abuse. Behav Genet 41:787-802
Shimamoto, Akiko; Debold, Joseph F; Holly, Elizabeth N et al. (2011) Blunted accumbal dopamine response to cocaine following chronic social stress in female rats: exploring a link between depression and drug abuse. Psychopharmacology (Berl) 218:271-9
Takahashi, Aki; Shimamoto, Akiko; Boyson, Christopher O et al. (2010) GABA(B) receptor modulation of serotonin neurons in the dorsal raphé nucleus and escalation of aggression in mice. J Neurosci 30:11771-80
van Erp, A M; Tachi, N; Miczek, K A (2001) Short or continuous social stress: suppression of continuously available ethanol intake in subordinate rats. Behav Pharmacol 12:335-42
Mandillo, S; Titchen, K; Miczek, K A (1998) Ethanol drinking in socially housed squirrel monkeys. Behav Pharmacol 9:363-7
van Erp, A M; Miczek, K A (1997) Increased aggression after ethanol self-administration in male resident rats. Psychopharmacology (Berl) 131:287-95
Miczek, K A; Haney, M (1994) Psychomotor stimulant effects of d-amphetamine, MDMA and PCP: aggressive and schedule-controlled behavior in mice. Psychopharmacology (Berl) 115:358-65
Haney, M; Miczek, K A (1994) Ultrasounds emitted by female rats during agonistic interactions: effects of morphine and naltrexone. Psychopharmacology (Berl) 114:441-8
Miczek, K A; Weerts, E; Haney, M et al. (1994) Neurobiological mechanisms controlling aggression: preclinical developments for pharmacotherapeutic interventions. Neurosci Biobehav Rev 18:97-110
Tornatzky, W; Miczek, K A (1994) Behavioral and autonomic responses to intermittent social stress: differential protection by clonidine and metoprolol. Psychopharmacology (Berl) 116:346-56

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