Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA
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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 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).
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”.
KeywordsStress Locomotor sensitization Escalated cocaine self-administration CRF-R1 CP 154,526 VTA
- Iwasaki-Sekino A, Mano-Otagiri A, Ohata H, Yamauchi N, Shibasaki T (2009) Gender differences in corticotropin and corticosterone secretion and corticotropin-releasing factor mRNA expression in the paraventricular nucleus of the hypothalamus and the central nucleus of the amygdala in response to footshock stress or psychological stress in rats. Psychoneuroendocrinology 34:226–237PubMedCrossRefGoogle Scholar
- Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 3rd edn. Academic, San DiegoGoogle Scholar
- Remie R, van Dongen JJ, Rensema JW (1990) Permanent cannulation of the jugular vein (acc. to Steffens). In: van Dongen JJ (ed) Manual of microsurgery on the laboratory rat. Elsevier, Amsterdam, pp 159–169Google Scholar
- Sauvage M, Steckler T (2001) Detection of corticotropin-releasing hormone receptor 1 immunoreactivity in cholinergic, dopaminergic and noradrenergic neurons of the murine basal forebrain and brainstem nuclei-potential implication for arousal and attention. Neuroscience 104:643–652PubMedCrossRefGoogle Scholar
- Schulz DW, Mansbach RS, Sprouse J, Braselton JP, Collins J, Corman M, Dunaiskis A, Faraci S, Schmidt AW, Seeger T, Seymour P, Tingley FD III, Winston EN, Chen YL, Heym J (1996) CP-154,526: a potent and selective nonpeptide antagonist of corticotropin releasing factor receptors. Proc Natl Acad Sci USA 93:10477–10482PubMedCrossRefGoogle Scholar
- Shaham Y, Funk D, Erb S, Brown TJ, Walker C, Stewart J (1997) Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 17:0–4Google Scholar
- Substance Abuse and Mental Health Services Administration (2010) Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of national findings. US Department of Health and Human Services, RockvilleGoogle Scholar