Affective and neuroendocrine effects of withdrawal from chronic, long-acting opiate administration

Hamilton, Kathryn L.; Harris, Andrew C.; Gewirtz, Jonathan C.

doi:10.1016/j.brainres.2013.09.026

Cited by 10 publications

(5 citation statements)

References 60 publications

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“…Stress may have therefore influenced nicotine discrimination had a 0.4 mg/kg dose of nicotine been tested. Given that numerous behaviorallyrelevant hormones or neurotransmitters exhibit circadian rhythmicity (e.g., corticosterone, dopamine, see Hamilton et al, 2013; McClung, 2007), the fact that animals were tested during different phases of the light/dark cycle in Experiments 1 and 2 could also account for the different effects of stress across studies.…”

Section: Discussionmentioning

confidence: 99%

Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

Harris¹,

Mattson²,

Shelley³

et al. 2014

Pharmacology Biochemistry and Behavior

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Stress enhances the locomotor stimulant and discriminative stimulus effects of several addictive drugs (e.g., morphine) in rodents, yet interactions between stress and nicotine’s effects in these behavioral models have not been well established. To this end, the current studies examined the effects of restraint stress on nicotine-induced locomotor activity and nicotine discrimination in rats. We used a novel approach in which onset of stress and nicotine administration occurred concurrently (i.e., simultaneous exposure) to simulate effects of stress on ongoing tobacco use, as well as a more traditional approach in which a delay was imposed between stress and nicotine administration (i.e., sequential exposure). Simultaneous exposure to stress reduced the rate of locomotor sensitization induced by daily injections of nicotine (0.4 mg/kg, s.c.). A lower dose of nicotine (0.1 mg/kg, s.c.) produced modest effects on activity that were generally unaffected by simultaneous exposure to stress. Sequential exposure to stress and nicotine (0.4 mg/kg, s.c.) slightly suppressed nicotine-induced activity, but did not influence rate of locomotor sensitization. Neither simultaneous nor sequential exposure to stress influenced the discriminative stimulus effects of nicotine (0.01 – 0.2 mg/kg, s.c.). These data show that restraint stress reduces nicotine’s locomotor stimulant effects, particularly when onset of stress and nicotine exposure occurs simultaneously, but does not influence nicotine discrimination. These findings contrast with the ability of stress to enhance the effects of other drugs in these models. This study also suggests that studying the influence of simultaneous stress exposure on drug effects may be useful for understanding the role of stress in addiction.

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Section: Discussionmentioning

confidence: 99%

Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

Harris¹,

Mattson²,

Shelley³

et al. 2014

Pharmacology Biochemistry and Behavior

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“…Offspring prenatally exposed to methadone exhibited increased blood levels of the stress hormone corticosterone compared with those in both the vehicle-and buprenorphineexposed offspring. This finding may be explained by the more rapid elimination of methadone and may therefore be a sign of opioid withdrawal (Hamilton et al, 2013);but it may also be due to the methadone exposure itself (Bartolome and Kuhn, 1983). USVs, which are used as a measure of withdrawal in rodents (Barr et al, 1998), were not significantly different between the groups; however, the number of calls varied considerably between individual pups, especially in the opioid-treated groups, where approximately 50% of the methadone-and buprenorphine-exposed offspring exhibited increased vocalizations on PND 7.…”

Section: /119 5/111 2/99mentioning

confidence: 99%

High Accumulation of Methadone Compared with Buprenorphine in Fetal Rat Brain after Maternal Exposure

Kongstorp

Bogen

Stiris

et al. 2019

J Pharmacol Exp Ther

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Experimental animal studies are valuable in revealing a causal relationship between prenatal exposure to opioid maintenance treatment (OMT) and subsequent effects; however, previous animal studies of OMT during pregnancy have been criticized for their lack of clinical relevance because of their use of high drug doses and the absence of pharmacokinetic data. Hence, the aim of this study was to determine blood and brain concentrations in rat dams, fetuses, and offspring after continuous maternal exposure to methadone or buprenorphine during gestation and to examine the offspring for neonatal outcomes and withdrawal symptoms. Female rats were implanted with a 28-day osmotic minipump delivering methadone (10 mg/kg per day), buprenorphine (1 mg/kg per day) or vehicle 5 days before mating. Continuous exposure to methadone or buprenorphine induced stable blood concentrations in the dams of 0.25 6 0.02 mM and 5.65 6 0.16 nM, respectively. The fetal brain concentration of methadone (1.89 6 0.35 nmol/g) was twice as high as that in the maternal brain, whereas the fetal brain concentration of buprenorphine (20.02 6 4.97 pmol/g) was one-third the maternal brain concentration. The opioids remained in the offspring brain several days after the exposure ceased. Offspring prenatally exposed to methadone, but not buprenorphine, displayed reduced body weight and length and increased corticosterone levels. No significant changes in ultrasonic vocalizations were revealed. Our data in rat fetuses and neonates indicate that OMT with buprenorphine may be a better choice than methadone during pregnancy. SIGNIFICANCE STATEMENT Concern has been raised about the use of opioid maintenance treatment during pregnancy because of the important role of the endogenous opioid system in brain development. Here, we show that the methadone concentration in the fetal rat brain was twice as high as that in the maternal brain, whereas the buprenorphine concentration was one-third the maternal concentration. Furthermore, buprenorphine allowed more favorable birth outcomes, suggesting that buprenorphine may be a better choice during pregnancy.

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“…They trigger compulsive drug use, drug-seeking behavior, and relapse [ 9 ]. Individuals suffering with substance abuse disorder often experience comorbid mental disorders; therefore, the emotional disturbances of withdrawal can worsen pre-existing mental disorders, which, in turn, may contribute further to a cycle of increased drug use [ 10 ]. A literature search by Ahmed et al (2023) examines the vulnerabilities that exist within psychoactive substance use, including heritable alterations of epigenetic biomarkers in both clinical and preclinical models [ 11 ].…”

Section: Drugs Of Abuse: Mechanisms Of Actionmentioning

confidence: 99%

The Role of Estrogen Signaling and Exercise in Drug Abuse: A Review

Ahmed,

Zyla,

Hammond

et al. 2024

Clinics and Practice

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Background: Discovering how sex differences impact the efficacy of exercise regimens used for treating drug addiction is becoming increasingly important. Estrogen is a hormone believed to explain a large portion of sex differences observed during drug addiction, and why certain exercise regimens are not equally effective between sexes in treatment. Addiction is currently a global hindrance to millions, many of whom are suffering under the influence of their brain’s intrinsic reward system coupled with external environmental factors. Substance abuse disorders in the U.S. alone cost billions of dollars annually. Review Summary: Studies involving the manipulation of estrogen levels in female rodents, primarily via ovariectomy, highlight its impact regarding drug addiction. More specifically, female rodents with higher estrogen levels during the estrus phase increase cocaine consumption, whereas those in the non-estrus phase (low estrogen levels) decrease cocaine consumption. If estrogen is reintroduced, self-administration increases once again. Exercise has been proven to decrease relapse tendency, but its effect on estrogen levels is not fully understood. Conclusions: Such findings and results discussed in this review suggest that estrogen influences the susceptibility of females to relapse. Therefore, to improve drug-abuse-related treatment, exercise regimens for females should be generated based on key sex differences with respect to males.

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Affective and neuroendocrine effects of withdrawal from chronic, long-acting opiate administration

Cited by 10 publications

References 60 publications

Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

Restraint stress attenuates nicotine's locomotor stimulant but not discriminative stimulus effects in rats

High Accumulation of Methadone Compared with Buprenorphine in Fetal Rat Brain after Maternal Exposure

The Role of Estrogen Signaling and Exercise in Drug Abuse: A Review

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