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Psychopharmacology (Berl). 2011 Nov;218(1):257-69. doi: 10.1007/s00213-011-2266-8. Epub 2011 Apr 6.

Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA.

Author information

1
Department of Psychology, Tufts University, Medford, MA, USA. christopher.boyson@tufts.edu

Abstract

RATIONALE:

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.

OBJECTIVE:

The study aims to prevent the effects of intermittently scheduled, brief social defeat stress on subsequent intravenous (IV) cocaine self-administration by pretreatment with a CRF receptor subtype 1 (CRF-R1) antagonist.

MATERIALS AND METHODS:

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).

RESULTS:

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".

CONCLUSIONS:

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".

PMID:
21468623
PMCID:
PMC3166547
DOI:
10.1007/s00213-011-2266-8
[Indexed for MEDLINE]
Free PMC Article

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