Sex Differences in the Neural Mechanisms Mediating Addiction: a New Synthesis and Hypothesis

Overview

Journal Biol Sex Differ

Publisher Biomed Central

Specialties Biology
Physiology

Date 2012 Jun 9

PMID 22676718

Citations 159

Authors

Jill B Becker

Adam N Perry

Christel Westenbroek

Affiliations

Soon will be listed here.

Abstract

In this review we propose that there are sex differences in how men and women enter onto the path that can lead to addiction. Males are more likely than females to engage in risky behaviors that include experimenting with drugs of abuse, and in susceptible individuals, they are drawn into the spiral that can eventually lead to addiction. Women and girls are more likely to begin taking drugs as self-medication to reduce stress or alleviate depression. For this reason women enter into the downward spiral further along the path to addiction, and so transition to addiction more rapidly. We propose that this sex difference is due, at least in part, to sex differences in the organization of the neural systems responsible for motivation and addiction. Additionally, we suggest that sex differences in these systems and their functioning are accentuated with addiction. In the current review we discuss historical, cultural, social and biological bases for sex differences in addiction with an emphasis on sex differences in the neurotransmitter systems that are implicated.

Citing Articles

Methamphetamine self-administration causes neuronal dysfunction in rat medial prefrontal cortex in a sex-specific and withdrawal time-dependent manner.

Chen L, Kreko-Pierce T, Cassoday S, Al-Harthi L, Hu X Front Pharmacol. 2025; 16:1527795.

PMID: 40028159 PMC: 11868113. DOI: 10.3389/fphar.2025.1527795.

Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.

Van Doorn C, Zelows M, Jaramillo A Front Neurosci. 2025; 19:1545810.

PMID: 39975969 PMC: 11835941. DOI: 10.3389/fnins.2025.1545810.

Sex differences in dorsal striatal volume and interest in quitting smoking.

Huang S, MacLean R, Beltz A, McClernon F, Kozink R, Wilson S Drug Alcohol Depend. 2025; 267:112543.

PMID: 39764928 PMC: 11771478. DOI: 10.1016/j.drugalcdep.2024.112543.

A protocol for modifying progesterone to increase postpartum cigarette smoking abstinence and reduce secondhand smoke exposure in infants.

Abdelwahab N, Allen A, Harrison K, Petersen A, Allen S Contemp Clin Trials Commun. 2024; 42:101389.

PMID: 39618477 PMC: 11607600. DOI: 10.1016/j.conctc.2024.101389.

Understanding the Emergence of Comorbidity between Problematic Online Gaming and Gambling: A Network Analysis Approach.

Bloch M, Misiak B Brain Sci. 2024; 14(9).

PMID: 39335424 PMC: 11444146. DOI: 10.3390/brainsci14090929.

References

Wise R, Morales M . A ventral tegmental CRF-glutamate-dopamine interaction in addiction. Brain Res. 2009; 1314:38-43. PMC: 2819620. DOI: 10.1016/j.brainres.2009.09.101. View

Bobzean S, Dennis T, Addison B, Perrotti L . Influence of sex on reinstatement of cocaine-conditioned place preference. Brain Res Bull. 2010; 83(6):331-6. DOI: 10.1016/j.brainresbull.2010.09.003. View

Bie B, Zhu W, Pan Z . Rewarding morphine-induced synaptic function of delta-opioid receptors on central glutamate synapses. J Pharmacol Exp Ther. 2009; 329(1):290-6. PMC: 2670596. DOI: 10.1124/jpet.108.148908. View

Koob G, Kreek M . Stress, dysregulation of drug reward pathways, and the transition to drug dependence. Am J Psychiatry. 2007; 164(8):1149-59. PMC: 2837343. DOI: 10.1176/appi.ajp.2007.05030503. View

Threlfell S, Clements M, Khodai T, Pienaar I, Exley R, Wess J . Striatal muscarinic receptors promote activity dependence of dopamine transmission via distinct receptor subtypes on cholinergic interneurons in ventral versus dorsal striatum. J Neurosci. 2010; 30(9):3398-408. PMC: 2866006. DOI: 10.1523/JNEUROSCI.5620-09.2010. View

Diver M, Imtiaz K, Ahmad A, Vora J, Fraser W . Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol (Oxf). 2003; 58(6):710-7. DOI: 10.1046/j.1365-2265.2003.01772.x. View

Thompson T, Moss R . Estrogen regulation of dopamine release in the nucleus accumbens: genomic- and nongenomic-mediated effects. J Neurochem. 1994; 62(5):1750-6. DOI: 10.1046/j.1471-4159.1994.62051750.x. View

Randall-Thompson J, Pescatore K, Unterwald E . A role for delta opioid receptors in the central nucleus of the amygdala in anxiety-like behaviors. Psychopharmacology (Berl). 2010; 212(4):585-95. PMC: 3990196. DOI: 10.1007/s00213-010-1980-y. View

Consolo S, Caltavuturo C, Colli E, Recchia M, Di Chiara G . Different sensitivity of in vivo acetylcholine transmission to D1 receptor stimulation in shell and core of nucleus accumbens. Neuroscience. 1999; 89(4):1209-17. DOI: 10.1016/s0306-4522(98)00309-1. View

10.

Torres-Hernandez A, Gonzalez-Vegas J . Effects of 17beta-estradiol on the spontaneous activity of substantia nigra neurons: evidence for a non-genomic mechanism. Brain Res. 2005; 1049(1):1-7. DOI: 10.1016/j.brainres.2005.04.085. View

11.

Fleming A, Corter C, Stallings J, Steiner M . Testosterone and prolactin are associated with emotional responses to infant cries in new fathers. Horm Behav. 2002; 42(4):399-413. DOI: 10.1006/hbeh.2002.1840. View

12.

Hilakivi-Clarke L, Corduban T, Taira T, Hitri A, Deutsch S, Korpi E . Alterations in brain monoamines and GABAA receptors in transgenic mice overexpressing TGF alpha. Pharmacol Biochem Behav. 1995; 50(4):593-600. DOI: 10.1016/0091-3057(94)00347-5. View

13.

Naylor J, Li Q, Kang-Park M, Wilson W, Kuhn C, Moore S . Dopamine attenuates evoked inhibitory synaptic currents in central amygdala neurons. Eur J Neurosci. 2010; 32(11):1836-42. PMC: 2994996. DOI: 10.1111/j.1460-9568.2010.07457.x. View

14.

Plebani J, Lynch K, Yu Q, Pettinati H, OBrien C, Kampman K . Results of an initial clinical trial of varenicline for the treatment of cocaine dependence. Drug Alcohol Depend. 2011; 121(1-2):163-6. PMC: 3262950. DOI: 10.1016/j.drugalcdep.2011.08.025. View

15.

Alheid G . Extended amygdala and basal forebrain. Ann N Y Acad Sci. 2003; 985:185-205. DOI: 10.1111/j.1749-6632.2003.tb07082.x. View

16.

Lindskog M, Svenningsson P, Fredholm B, Greengard P, Fisone G . Mu- and delta-opioid receptor agonists inhibit DARPP-32 phosphorylation in distinct populations of striatal projection neurons. Eur J Neurosci. 1999; 11(6):2182-6. DOI: 10.1046/j.1460-9568.1999.00597.x. View

17.

Cicero T, Aylward S, Meyer E . Gender differences in the intravenous self-administration of mu opiate agonists. Pharmacol Biochem Behav. 2003; 74(3):541-9. DOI: 10.1016/s0091-3057(02)01039-0. View

18.

Weiss F, Markou A, Lorang M, Koob G . Basal extracellular dopamine levels in the nucleus accumbens are decreased during cocaine withdrawal after unlimited-access self-administration. Brain Res. 1992; 593(2):314-8. DOI: 10.1016/0006-8993(92)91327-b. View

19.

Hecht G, Spear N, Spear L . Changes in progressive ratio responding for intravenous cocaine throughout the reproductive process in female rats. Dev Psychobiol. 1999; 35(2):136-45. View

20.

Lejuez C, Bornovalova M, Reynolds E, Daughters S, Curtin J . Risk factors in the relationship between gender and crack/cocaine. Exp Clin Psychopharmacol. 2007; 15(2):165-75. PMC: 3182264. DOI: 10.1037/1064-1297.15.2.165. View