Neurological Mechanisms of Aggression, Anxiety & Stress
The Miczek psychopharmacology laboratory studies brain mechanisms of aggression, anxiety, social stress, and abuse of alcohol and other drugs, integrating behavioral, physiological, and neuropharmacological research strategies.
Corticotrophin Releasing Factor and Social Stress
One of our ongoing projects focuses on the role of corticotrophin releasing factor (CRF) in the relationship between social stress and cocaine self-administration. Microinjection studies (see Boyson, et al, 2011 ) reveal that CRF receptor 1 (CRF-R1) in the ventral tegmental area (VTA) is a major contributor to excessive cocaine intake during a 24-hour unlimited access “binge” (Fig 1).
Figure 1. Effects of intra-VTA microinjection of CP154, 526 . Pretreatment with a CRF-R1 antagonist (0.3 μg/0.5 μl/side) into the VTA prior to each social defeat episode prevented stress-induced locomotor sensitization to a cocaine challenge and prevented escalated cocaine self-administration during a 24-h binge.
Coping with Social Stress
We are also interested in sex differences in coping with brief episodic or continuous social stress and CRF modulation of dopamine in rodent models of cocaine abuse. Episodes of social stress sensitize males and females behaviorally and in accumbens dopamine. Learn more about this work in Shimamoto, et al, 2011 .
Figure 2. Dopamine in N accumbens shell during social stress in females. Ten days after the last confrontation in a 21 day stress protocol, the experimental rat was challenged with 10 mg/kg of cocaine, and levels of DA and 5-HT in the NAc were measured using in vivo microdialysis.
Another area of investigation involves study of extrahypothalamic stress neuropeptides in escalated alcohol drinking during repeated cycles of intermittent access periods and during withdrawal from alcohol as potential mechanisms of dependence.
Role of NMDA and GABAA Receptors in Aggressive Behavior
Our group is also interested in the role NMDA and GABAA receptors play in the escalation of aggression by alcohol and benzodiazepines. Benzodiazepine-escalated aggression is being evaluated using benzodiazepine-insensitive GABAA α1, α2, or α3 receptor knock-in mutants and their wild-type C57BL/6J counterparts.