Sex differences in affective response to opioid withdrawal during adolescence

Hodgson, Stephen R.; Hofford, Rebecca S.; Roberts, Kris W.; Eitan, Dvora; Wellman, Paul J.; Eitan, Shoshana

doi:10.1177/0269881109106976

Cited by 16 publications

(7 citation statements)

References 46 publications

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“…It is also known that major neurobiological effects of drugs of abuse, including MOPr agonists, cocaine, alcohol and cannabis can be sexually dimorphic . Some preclinical studies have also reported that exposure to specific drugs of abuse has sexually dimorphic depressant‐like effects . Overall, this analysis confirms that women with either opioid or cocaine dependence diagnoses have greater odds of depression comorbidity than men.…”

Section: Discussionsupporting

confidence: 70%

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

et al. 2017

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Background and Objectives Addictions to heroin or to cocaine are associated with substantial psychiatric comorbidity, including depression. Poly-drug self-exposure (e.g., to heroin, cocaine, cannabis or alcohol) is also common, and may further affect depression comorbidity. Methods This case-control study examined the relationship of exposure to the above drugs and depression comorbidity. Participants were recruited from methadone maintenance clinics, and from the community. Adult male and female participants (n=1,201) were ascertained consecutively by experienced licensed clinicians. The instruments used were the SCID-I, and Kreek-McHugh-Schluger-Kellogg (KMSK) scales, which provide a rapid dimensional measure of maximal lifetime self-exposure to each of the above drugs. This measure ranges from no exposure to high unit dose, high frequency, and long duration of exposure. Results A multiple logistic regression with stepwise variable selection revealed that increasing exposure to heroin or to cocaine was associated greater odds of depression, with all cases and controls combined. In cases with an opioid dependence diagnosis, increasing cocaine exposure was associated with a further increase in odds of depression. However, in cases with a cocaine dependence diagnosis, increasing exposure to either cannabis or alcohol, as well as heroin, was associated with a further increase in odds of depression. Discussion and Conclusions This dimensional analysis of exposure to specific drugs provides insights on depression comorbidity with addictive diseases, and the impact of poly-drug exposure. Scientific Significance A rapid analysis of exposure to drugs of abuse reveals how specific patterns of drug and poly-drug exposure are associated with increasing odds of depression.

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Section: Discussionsupporting

confidence: 70%

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

et al. 2017

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“…Furthermore, the paraventricular nucleus of the thalamus mediates the aversive effects of opiate withdrawal through connections with the nucleus accumbens (Zhu et al 2016 ). Because juveniles are less sensitive to the aversive effects of withdrawal than adults (Doremus-Fitzwater and Spear 2007 ; Hodgson et al 2010 ) it is plausible that denser MOR binding allows for higher MOR activation in the paraventricular thalamic nucleus, which in turn may inhibit signaling in this pathway, resulting in reduced withdrawal symptoms in juveniles. These hypotheses will need to be tested in future studies.…”

Section: Discussionmentioning

confidence: 99%

Robust age, but limited sex, differences in mu-opioid receptors in the rat brain: relevance for reward and drug-seeking behaviors in juveniles

2017

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In the brain, the µ-opioid receptor (MOR) is involved in reward-seeking behaviors and plays a pivotal role in the mediation of opioid use disorders. Furthermore, reward-seeking behaviors and susceptibility to opioid addiction are particularly evident during the juvenile period, with a higher incidence of opioid use in males and higher sensitivity to opioids in females. Despite these age and sex differences in MOR-mediated behaviors, little is known regarding potential age and sex differences in the expression of MORs in the brain. Here, we used receptor autoradiography to compare MOR binding densities between juvenile and adult male and female rats. Age differences were found in MOR binding density in 12 out of 33 brain regions analyzed, with 11 regions showing higher MOR binding density in juveniles than in adults. These include the lateral septum, as well as sub-regions of the bed nucleus of the stria terminalis, hippocampus, and thalamus. Sex differences in MOR binding density were observed in only two brain regions, namely, the lateral septum (higher in males) and the posterior cortical nucleus of the amygdala (higher in females). Overall, these findings provide an important foundation for the generation of hypotheses regarding differential functional roles of MOR activation in juveniles versus adults. Specifically, we discuss the possibility that higher MOR binding densities in juveniles may allow for higher MOR activation, which could facilitate behaviors that are heightened during the juvenile period, such as reward and drug-seeking behaviors.

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“…On days 5 and 6, they were injected with 40 mg/kg morphine or saline. This morphine regimen was selected based on both our previous studies (Buckman et al, 2009; Eitan et al, 2003; Hodgson et al, 2008; Hodgson et al, 2009a; Hodgson et al, 2010; Hodgson et al, 2009b) as well as other investigators (Contet et al, 2008; el-kadi and Sharif, 1994; Kest et al, 2001; Matthes et al, 1996; Spanagel et al, 1994) demonstrating that such doses induce significant antinociceptive tolerance, sensitization, dependence and withdrawal. Following the injections, mice were returned to their respective home cages.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, there are sex-specific differences in the potency or efficacy of opioids as reinforcers, where females are more vulnerable to the acquisition of opioids, administer larger quantities, and work harder to obtain it (Cicero et al, 2003; Lynch and Carroll, 1999). Furthermore, differences in the emotional response to morphine withdrawal were observed between male and female mice (Hodgson et al, 2009a; Hodgson et al, 2009b). Given sex-related differences in both social interactions and in the responses to morphine, this study examines vulnerabilities to social influences on morphine locomotor sensitization in female adolescent mice.…”

Section: Introductionmentioning

confidence: 99%

Social influences on morphine sensitization in adolescent females

Hofford¹,

Roberts²,

Wellman³

et al. 2010

Drug and Alcohol Dependence

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We recently observed that social interactions influence morphine responsiveness in adolescent males. Given sex-related differences in both social interactions and responses to morphine, the present study examines social influences on morphine sensitization in adolescent female mice. Four experimental groups were examined: [1] morphine-treated mice (twice daily, 10-40 mg/kg, s.c.) housed physically and visually separated from saline-treated mice ('morphine only'), [2] morphine-treated mice housed together with saline-treated mice ('morphine cage-mates (of saline)'), [3] saline-treated mice housed together with morphine-treated mice ('saline cage-mates (of morphine)'), and [4] saline-treated mice housed physically and visually separated from morphine-treated mice ('saline only'). Following the treatment period, mice were tested individually for their locomotor response to 20 mg/kg morphine (s.c.). There were no significant differences in morphine-induced hyper-locomotion between saline only and saline cage-mates (of morphine) female adolescent mice. Notably, morphine only mice exhibited significantly greater morphine sensitization as compared to morphine cage-mates (of saline). Thus, this study demonstrates social influences on morphine sensitization in adolescent females. Drug use during early adolescence is a key predictor of later drug abuse and dependence during adulthood. Thus, understanding the specific vulnerabilities to drug use in this age group may represent a first step in helping develop more effective treatment programs.

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Sex differences in affective response to opioid withdrawal during adolescence

Cited by 16 publications

References 46 publications

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

Can a rapid measure of self-exposure to drugs of abuse provide dimensional information on depression comorbidity?

Robust age, but limited sex, differences in mu-opioid receptors in the rat brain: relevance for reward and drug-seeking behaviors in juveniles

Social influences on morphine sensitization in adolescent females

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