Differential Effects of Allopregnanolone on the Escalation of Cocaine Self-administration and Sucrose Intake in Female Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2010 Aug 7

PMID 20689941

Citations 21

Authors

Justin J Anker

Natalie E Zlebnik

Marilyn E Carroll

Affiliations

Soon will be listed here.

Abstract

Rationale: Evidence suggests that the progesterone metabolite allopregnanolone (ALLO) decreases cocaine seeking in animal models of relapse.

Objective: The purpose of this study was to examine the effects of ALLO on an animal model of cocaine and sucrose bingeing (escalation). Allopregnanolone's effects on yohimbine-induced sucrose intake were also examined. In a separate group of animals, dose interactions between ALLO and cocaine were examined with an abbreviated procedure, a short access progressive ratio (PR) schedule for cocaine reinforcement.

Methods: Female rats were treated with ALLO (15 mg/kg, s.c.) or vehicle (VEH) and trained to lever press for cocaine infusions (0.4 mg/kg) under an extended-access procedure. In a separate condition, other ALLO- and VEH-treated female rats self-administered orally delivered liquid sucrose. Allopregnanolone and VEH treatment was then discountinued and the sucrose-maintained rats were administered priming injections of saline, yohimbine, or yohimbine + ALLO. For the PR condition, rats were first treated with VEH until reaching stability at four doses of cocaine (0.2, 0.4, 0.8, and 1.6 mg/kg in mixed order). Subsequently, rats re-established their baseline cocaine intake at the four cocaine doses following treatment with each of two counterbalanced doses of ALLO (15 and 30 mg/kg).

Results: ALLO significantly blocked the escalation of cocaine self-administration but did not reliably affect intake of sucrose under a similar condition or affect cocaine intake at several doses under a PR schedule. Yohimbine significantly increased sucrose intake while ALLO failed to attenuate this increase.

Conclusion: These findings indicate that ALLO protects against binge-like patterns of cocaine intake but does not reduce sugar intake that is acutely increased by yohimbine in females.

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References

Reddy D, Kulkarni S . Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats. Pharmacol Biochem Behav. 1999; 62(1):53-60. DOI: 10.1016/s0091-3057(98)00126-9. View

Romeo E, Brancati A, De Lorenzo A, FUCCI P, Furnari C, Pompili E . Marked decrease of plasma neuroactive steroids during alcohol withdrawal. Clin Neuropharmacol. 1996; 19(4):366-9. DOI: 10.1097/00002826-199619040-00011. View

Brunton P, McKay A, Ochedalski T, Piastowska A, Rebas E, Lachowicz A . Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009; 29(20):6449-60. PMC: 6665894. DOI: 10.1523/JNEUROSCI.0708-09.2009. View

Anker J, Carroll M . The role of progestins in the behavioral effects of cocaine and other drugs of abuse: human and animal research. Neurosci Biobehav Rev. 2010; 35(2):315-33. PMC: 3243052. DOI: 10.1016/j.neubiorev.2010.04.003. View

Higgs S, Cooper S . Antineophobic effect of the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one in male rats. Pharmacol Biochem Behav. 1998; 60(1):125-31. DOI: 10.1016/s0091-3057(97)00562-5. View

Karila L, Gorelick D, Weinstein A, Noble F, Benyamina A, Coscas S . New treatments for cocaine dependence: a focused review. Int J Neuropsychopharmacol. 2007; 11(3):425-38. DOI: 10.1017/S1461145707008097. View

Carroll M, Boe I . Increased intravenous drug self-administration during deprivation of other reinforcers. Pharmacol Biochem Behav. 1982; 17(3):563-7. DOI: 10.1016/0091-3057(82)90319-7. View

Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman M . Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology. 2004; 145(8):3754-62. DOI: 10.1210/en.2004-0305. View

Edler C, Lipson S, Keel P . Ovarian hormones and binge eating in bulimia nervosa. Psychol Med. 2006; 37(1):131-41. DOI: 10.1017/S0033291706008956. View

10.

Morgan D, Roberts D . Sensitization to the reinforcing effects of cocaine following binge-abstinent self-administration. Neurosci Biobehav Rev. 2004; 27(8):803-12. DOI: 10.1016/j.neubiorev.2003.11.004. View

11.

Sofuoglu M, Babb D, Hatsukami D . Effects of progesterone treatment on smoked cocaine response in women. Pharmacol Biochem Behav. 2002; 72(1-2):431-5. DOI: 10.1016/s0091-3057(02)00716-5. View

12.

Rada P, Avena N, Hoebel B . Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience. 2005; 134(3):737-44. DOI: 10.1016/j.neuroscience.2005.04.043. View

13.

Grilo C, Shiffman S, Wing R . Relapse crises and coping among dieters. J Consult Clin Psychol. 1989; 57(4):488-95. DOI: 10.1037//0022-006x.57.4.488. View

14.

Perrotti L, Russo S, Fletcher H, Chin J, Webb T, Jenab S . Ovarian hormones modulate cocaine-induced locomotor and stereotypic activity. Ann N Y Acad Sci. 2001; 937:202-16. DOI: 10.1111/j.1749-6632.2001.tb03566.x. View

15.

Sofuoglu M, Nelson D, Pentel P, Hatsukami D . Sex and menstrual cycle differences in the subjective effects from smoked cocaine in humans. Exp Clin Psychopharmacol. 1999; 7(3):274-83. DOI: 10.1037//1064-1297.7.3.274. View

16.

Shoptaw S, Yang X, Rotheram-Fuller E, Hsieh Y, Kintaudi P, Charuvastra V . Randomized placebo-controlled trial of baclofen for cocaine dependence: preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry. 2004; 64(12):1440-8. DOI: 10.4088/jcp.v64n1207. View

17.

Giorgetti M, Javaid J, Davis J, Costa E, Guidotti A, Appel S . Imidazenil, a positive allosteric GABAA receptor modulator, inhibits the effects of cocaine on locomotor activity and extracellular dopamine in the nucleus accumbens shell without tolerance liability. J Pharmacol Exp Ther. 1998; 287(1):58-66. View

18.

Guo A, Petraglia F, Criscuolo M, Ficarra G, Nappi R, Palumbo M . Evidence for a role of neurosteroids in modulation of diurnal changes and acute stress-induced corticosterone secretion in rats. Gynecol Endocrinol. 1995; 9(1):1-7. DOI: 10.3109/09513599509160184. View

19.

Goeders J, Murnane K, Banks M, Fantegrossi W . Escalation of food-maintained responding and sensitivity to the locomotor stimulant effects of cocaine in mice. Pharmacol Biochem Behav. 2009; 93(1):67-74. PMC: 3523326. DOI: 10.1016/j.pbb.2009.04.008. View

20.

Dewey S, Chaurasia C, Chen C, Volkow N, Clarkson F, Porter S . GABAergic attenuation of cocaine-induced dopamine release and locomotor activity. Synapse. 1997; 25(4):393-8. DOI: 10.1002/(SICI)1098-2396(199704)25:4<393::AID-SYN11>3.0.CO;2-W. View