Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA.
Abstract: Intermittent exposure to social defeat stress can induce long-term
neural plasticity that may influence escalated cocaine-taking behavior. Stressful
encounters can lead to activation of dopamine neurons in the ventral tegmental area (VTA),
which are modulated by corticotropin releasing factor (CRF) neurons. The study aims to
prevent the effects of intermittently scheduled, brief soci... read moreal defeat stress on subsequent
intravenous (IV) cocaine self-administration by pretreatment with a CRF receptor subtype 1
(CRF-R1) antagonist. Long-Evans rats were submitted to four intermittent social defeat
experiences separated by 72 h over 10 days. Two experiments examined systemic or intra-VTA
antagonism of CRF-R1 subtype during stress on the later expression of locomotor
sensitization and cocaine self-administration during fixed (0.75 mg/kg/infusion) and
progressive ratio schedules of reinforcement (0.3 mg/kg/infusion), including a continuous
24-h "binge" (0.3 mg/kg/infusion). Pretreatment with a CRF-R1 antagonist, CP 154,526, (20
mg/kg i.p.) prior to each social defeat episode prevented the development of stress-induced
locomotor sensitization to a cocaine challenge and prevented escalated cocaine
self-administration during a 24-h "binge". In addition, 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". The current results
suggest that CRF-R1 subtype in the VTA is critically involved in the development of
stress-induced locomotor sensitization which may contribute to escalated cocaine
self-administration during continuous access in a 24-h "binge".
Thesis (M.S.)--Tufts University, 2011.
Submitted to the Dept. of Psychology.
Advisor: Klaus Miczek.
Committee: Joseph DeBold, and Stephen Heinrichs.
Keywords: Psychology, Psychobiology, and Behavioral sciences.read less