Abstract
Background
A history of brief intermittent social defeat stress can escalate cocaine self-administration and induce long-term adaptations in the mesolimbic dopamine system. Extra-hypothalamic corticotrophin releasing factor (CRF) has been shown to be closely associated with stress-induced escalation of drug use. How repeated stress modulates CRF release in the ventral tegmental area (VTA) and the roles of CRF receptors during different phases of stress-induced cocaine self-administration remain to be defined.
Objective
The current study examines the roles of CRF and CRF receptor 1 (CRFR1) in escalated intravenous cocaine self-administration after exposure to social defeat stress in mice.
Methods and results
First, CRFR1 antagonist (CP 376,395, 15 mg/kg, i.p.) given 30 min prior to each social defeat episode prevented later escalated cocaine self-administration. When CP 376,395 (5 and 15 mg/kg, i.p.) was administered 10 days after the last episode of social stress, the escalation of cocaine intake was dose-dependently reversed. Moreover, socially defeated mice showed increased CRF release in the VTA compared to controls. To further explore the role of CRFR1, CP 376,395 (0.5 and 1 μg/0.2 μl) was infused directly into the VTA before the cocaine self-administration session. Intra-VTA antagonism of CRFR1 was sufficient to reverse social defeat stress-escalated cocaine self-administration.
Conclusion
These findings suggest that CRF and CRFR1 exert multiple roles in the response to social stress that are relevant to escalated cocaine self-administration.
Similar content being viewed by others
References
Albrechet-Souza L, Hwa LS, Han X, Zhang EY, DeBold JF, Miczek KA (2015) Corticotropin releasing factor binding protein and CRF2 receptors in the ventral tegmental area: modulation of ethanol binge drinking in C57BL/6J mice. Alcohol Clin Exp Res 39:1609–1618
Björkqvist K (2001) Social defeat as a stressor in humans. Physiol Behav 73:435–442
Blacktop JM, Seubert C, Baker DA, Ferda N, Lee G, Graf EN, Mantsch JR (2011) Augmented cocaine seeking in response to stress or CRF delivered into the ventral tegmental area following long-access self-administration is mediated by CRF receptor type 1 but not CRF receptor type 2. J Neurosci 31:11396–11403
Borgland SL, Ungless MA, Bonci A (2010) Convergent actions of orexin/hypocretin and CRF on dopamine neurons: emerging players in addiction. Brain Res 1314:139–144
Bossert JM, Marchant NJ, Calu DJ, Shaham Y (2013) The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research. Psychopharmacology 229:453–476
Boyson CO, Holly EN, Shimamoto A, Albrechet-Souza L, Weiner LA, DeBold JF, Miczek KA (2014) Social stress and CRF-dopamine interactions in the VTA: role in long-term escalation of cocaine self-administration. J Neurosci 34:6659–6667
Boyson CO, Miguel TT, Quadros IM, DeBold JF, Miczek KA (2011) Prevention of social stress-escalated cocaine self-administration by CRF-R1 antagonist in the rat VTA. Psychopharmacology 218:257–269
Charlton BG, Ferrier IN, Perry RH (1987) Distribution of corticotropin-releasing factor-like immunoreactivity in human brain. Neuropeptides 10:329–334
Covington HE III, Miczek KA (2001) Repeated social-defeat stress, cocaine or morphine. Effects on behavioral sensitization and intravenous cocaine self-administration “binges”. Psychopharmacology 158:388–398
Cummings S, Elde R, Ells J, Lindall A (1983) Corticotropin-releasing factor immunoreactivity is widely distributed within the central nervous system of the rat: an immunohistochemical study. J Neurosci 3:1355–1368
Curtis AL, Pavcovich LA, Grigoriadis DE, Valentino RJ (1995) Previous stress alters corticotropin-releasing factor neurotransmission in the locus coeruleus. Neuroscience 65:541–550
Goeders NE, Guerin GF (2000) Effects of the CRH receptor antagonist CP-154,526 on intravenous cocaine self-administration in rats. Neuropsychopharmacology 23:577–586
Han X, Albrechet-Souza L, Doyle MR, Shimamoto A, DeBold JF, Miczek KA (2015) Social stress and escalated drug self-administration in mice II. Cocaine and dopamine in the nucleus accumbens. Psychopharmacology (Berl) 232:1003–1010
Hauger RL, Risbrough V, Brauns O, Dautzenberg FM (2006) Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets. CNS Neurol Disord Drug Targets 5:453–479
Heilig M, Koob GF (2007) A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci 30:399–406
Holly EN, Boyson CO, Montagud-Romero S, Stein DJ, Gobrogge KL, DeBold JF, Miczek KA (2016) Episodic social stress-escalated cocaine self-administration: role of phasic and tonic corticotropin releasing factor in the anterior and posterior ventral tegmental area. J Neurosci 36:4093–4105
Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G (2003) Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 24:580–588
Koob GF (2010) The role of CRF and CRF-related peptides in the dark side of addiction. Brain Res 1314:3–14
Koob GF, Zorrilla EP (2010) Neurobiological mechanisms of addiction: focus on corticotropin-releasing factor. Curr Opin Investig Drugs 11:63–71
Korotkova TM, Brown RE, Sergeeva OA, Ponomarenko AA, Haas HL (2006) Effects of arousal- and feeding-related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the rat. Eur J Neurosci 23:2677–2685
Kwako LE, Spagnolo PA, Schwandt ML, Thorsell A, George DT, Momenan R et al (2015) The corticotropin releasing hormone-1 (CRH1) receptor antagonist pexacerfont in alcohol dependence: a randomized controlled experimental medicine study. Neuropsychopharmacology 40:1053–1063
Mantsch JR, Baker DA, Funk D, Le AD, Shaham Y (2016) Stress-induced reinstatement of drug seeking: 20 years of progress. Neuropsychopharmacology 41:335–356
Manvich DF, Stowe TA, Godfrey JR, Weinshenker D (2016) A method for psychosocial stress-induced reinstatement of cocaine seeking in rats. Biol Psychiatry 79:940–946
Miczek KA, Nikulina EM, Shimamoto A, Covington HE III (2011) Escalated or suppressed cocaine reward, tegmental BDNF and accumbal dopamine due to episodic vs. continuous social stress in rats. J Neurosci 31:9848–9857
Miczek KA, O'Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Psychopharmacology 57:47–55
Miczek KA, Thompson ML, Shuster L (1982) Opioid-like analgesia in defeated mice. Science 215:1520–1522
Miczek KA, Yap JJ, Covington HE III (2008) Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake. Pharmacol Ther 120:102–128
National Research Council (2011) Guide for the care and use of laboratory animals, Eighth edn. National Academy Press, Washington DC
Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates, Second edn. Academic Press, San Diego
Piazza PV, Le Moal M (1998) The role of stress in drug self-administration. Trends Pharmacol Sci 19:67–74
Quadros IM, Miczek KA (2009) Two modes of intense cocaine bingeing: increased persistence after social defeat stress and increased rate of intake due to extended access conditions in rats. Psychopharmacology 206:109–121
Richter RM, Pich EM, Koob GF, Weiss F (1995) Sensitization of cocaine-stimulated increase in extracellular levels of corticotropin-releasing factor from the rat amygdala after repeated administration as determined by intracranial microdialysis. Neurosci Lett 187:169–172
Sarnyai Z, Shaham Y, Heinrichs SC (2001) The role of corticotropin-releasing factor in drug addiction. Pharmacol Rev 53:209–243
Schwandt ML, Cortes CR, Kwako LE, George DT, Momenan R, Sinha R et al (2016) The CRF1 antagonist verucerfont in anxious alcohol-dependent women: translation of neuroendocrine, but not of anti-craving effects. Neuropsychopharmacology 41:2818–2829
Shaham Y, de Wit H (2016) Lost in translation: CRF1 receptor antagonists and addiction treatment. Neuropsychopharmacology 41(12):2795–2797
Shaham Y, Funk D, Erb S, Brown TJ, Walker CD, Stewart J (1997) Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 17:2605–2614
Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158:343–359
Sinha R (2008) Chronic stress, drug use, and vulnerability to addiction. Ann N Y Acad Sci 1141:105–130
Snyder K, Wang WW, Han R, McFadden K, Valentino RJ (2012) Corticotropin-releasing factor in the norepinephrine nucleus, locus coeruleus, facilitates behavioral flexibility. Neuropsychopharmacology 37:520–530
Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186
Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378:287–292
Wanat MJ, Hopf FW, Stuber GD, Phillips PE, Bonci A (2008) Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J Physiol 586:2157–2170
Wang B, Shaham Y, Zitzman D, Azari S, Wise RA, You ZB (2005) Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: a role in stress-induced relapse to drug seeking. J Neurosci 25:5389–5396
Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225
Wise RA (1996) Neurobiology of addiction. Curr Opin Neurobiol 6(2):243–251
Yap JJ, Miczek KA (2007) Social defeat stress, sensitization, and intravenous cocaine self-administration in mice. Psychopharmacology 192:261–273
Zorrilla EP, Heilig M, de Wit H, Shaham Y (2013) Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism. Drug Alcohol Depend 128:175–186
Acknowledgements
This research was supported by National Institute on Drug Abuse Grant DA031734, KAM, PI.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Han, X., DeBold, J.F. & Miczek, K.A. Prevention and reversal of social stress-escalated cocaine self-administration in mice by intra-VTA CRFR1 antagonism. Psychopharmacology 234, 2813–2821 (2017). https://doi.org/10.1007/s00213-017-4676-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-017-4676-8