Gender differences in the intravenous self-administration of mu opiate agonists

Cicero, Theodore J.; Aylward, Shawn C.; Meyer, Edward R.

doi:10.1016/s0091-3057(02)01039-0

Cited by 179 publications

(124 citation statements)

References 28 publications

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“…Although a growing body of evidence suggests that females are more prone to drug self-administration than males (Alexander et al, 1978;Lynch and Carroll, 1999;Carroll et al, 2001;Cicero et al, 2003;Hu et al, 2004;Roth et al, 2004), we found no differences in the acquisition of male and female mice. However, it is noteworthy that choice accuracy for the morphine-reinforced arm of the maze reached a maximum in female WT mice, with over 95% of drug-reinforced responses for 4 out of 6 self-administration sessions.…”

Section: Discussioncontrasting

confidence: 93%

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

David

Matifas

Gavello-Baudy

et al. 2007

Neuropsychopharmacol

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Both m-opioid receptors (MORs) and d-opioid receptors (DORs) are expressed in the ventral tegmental area (VTA) and are thought to be involved in the addictive properties of opiates. However, their respective contributions to opiate reward remain unclear. We used intracranial self-administration (ICSA) to study the rewarding effects of morphine microinjections into the VTA of male and female MORÀ/À and DORÀ/À mice. In brains of mice tested for intra-VTA morphine self-administration, we analyzed regional Fos protein expression to investigate the neural circuitry underlying this behavior. Male and female WT and DORÀ/À mice exhibited similar selfadministration performances, whereas knockout of the MOR gene abolished intra-VTA morphine self-administration at all doses tested. Naloxone (4 mg/kg) disrupted this behavior in WT and DOR mutants, without triggering physical signs of withdrawal. Morphine ICSA was associated with an increase in Fos within the nucleus accumbens, striatum, limbic cortices, amygdala, hippocampus, the lateral mammillary nucleus (LM), and the ventral posteromedial thalamus (VPM). This latter structure was found to express high levels of Fos exclusively in self-administering WT and DORÀ/À mice. Abolition of morphine reward in MORÀ/À mice was associated with a decrease in Fos-positive neurons in the mesocorticolimbic dopamine system, amygdala, hippocampus (CA1), LM, and a complete absence within the VPM. We conclude that (i) VTA MORs, but not DORs, are critical for morphine reward and (ii) the role of VTA-thalamic projections in opiate reward deserves to be further explored.

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Section: Discussioncontrasting

confidence: 93%

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

David

Matifas

Gavello-Baudy

et al. 2007

Neuropsychopharmacol

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“…Although a preference for a chamber paired with morphine was conditioned in both groups, female rats exhibited a stronger preference for the morphine-paired chamber over a broader range of doses. Moreover, in a separate study (Cicero et al, 2003), female rats self-administered greater amounts of heroin and morphine under a fixed-ratio schedule of responding and showed higher "breakpoints" under a progressive ratio of responding compared to male rats.…”

Section: Discussionmentioning

confidence: 89%

Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

White

Michaels

Holtzman

2008

Pharmacology Biochemistry and Behavior

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Little has been done to investigate the effects of opioid exposure during adolescence. Therefore, our first objective was to determine behavioral differences in response to acutely administered morphine (e.g., antinociception and locomotion) between periadolescent and adult male and female rats. Our second objective was to determine the impact of age of morphine exposure on sensitivity to morphineinduced locomotion later in life. For the acute morphine studies, antinociceptive responses (using tail-flick and hot plate latencies) were assessed using cumulative morphine dosing (0.5-12 mg/kg) followed by a time course after the last morphine injection (up to 4 hr), and dose-response curves for motor activity (2 h test) were determined following saline and morphine (0.1-3.0 mg/kg) administration. For the long-term study, periadolescent and adult rats were given one of four treatment regimens (saline or one, three, or five days of morphine; 5.0 mg/kg, 2X/day). Changes in locomotor activity in response to saline or morphine (0.1-3.0 mg/kg) were determined one month later. A number of age-and sex-related behavioral differences were observed: basal differences in behavior were assay-dependent; however, male periadolescent rats were generally more sensitive to acute morphine-induced motor stimulation, while both male and female periadolescent rats tended to be less sensitive to morphine-induced antinociception. Lastly, following morphine exposure, activity was dependent on age of treatment and treatment regimen, with the greatest effects in fiveday periadolescent-treated animals. These findings demonstrate that the sensitivity of periadolescent rats to the acute and protracted effects of morphine is different from that of adult rats.

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“…34 It has been argued that these differences may in part be owing to sex differences in the reinforcing effects of nicotine, 35 and it is notable that there is growing evidence for sex differences in the activity of the opioid pathway. Several preclinical studies have indicated sex differences in opiate discrimination, self-administration and reward, [36][37][38] whereas sex has been reported to influence mu-opioid receptor binding in the human brain, 39 possibly mediated via differences in oestrogen-induced regulation. 40,41 More recently, the OPRM1 gene has been reported to be associated with the relative reinforcing value of nicotine in women, but not in men.…”

mentioning

confidence: 99%

Association of the mu-opioid receptor gene with smoking cessation

et al. 2007

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We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index (BMI) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy (NRT) patch or placebo in a randomized controlled trial, and were followed-up over an 8-year period following their initial cessation attempt. We also investigated possible sex differences in these relationships, given evidence for sex differences in smoking cessation and central opioid mechanisms, as well as some evidence for sex differences in response to NRT. Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment, with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch. Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt, with ex-smokers demonstrating an increase in BMI, and this increase being greater in female subjects than in male subjects. We did not observe any association of OPRM1 genotype with change in BMI, although there was a trend for genotype to influence the observed sex difference in change in BMI over time. Future studies should attempt to replicate these findings, and investigate the relationship between both short-and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes. Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption.

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Gender differences in the intravenous self-administration of mu opiate agonists

Cited by 179 publications

References 28 publications

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward

Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

Association of the mu-opioid receptor gene with smoking cessation

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