Chronic Heroin Self-Administration Desensitizes μ Opioid Receptor-Activated G-Proteins in Specific Regions of Rat Brain

Sim‐Selley, Laura J.; Selley, Dana E.; Vogt, Leslie J.; Childers, Steven R.; Martin, Thomas J.

doi:10.1523/jneurosci.20-12-04555.2000

Cited by 153 publications

(126 citation statements)

References 40 publications

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“…In the amygdala, it is not clear whether there is a direct interaction between AVP-producing cells and MOP-r activity. Despite an increased MOP-r binding density, earlier studies have found a decrease in MOP-r-stimulated G-protein (as reflected by GTPgS binding) in the rat amygdala after chronic heroin self-administration (Sim-Selley et al, 2000;Kruzich et al, 2003), suggesting involvement of amygdalar MOP-r desensitization in heroin dependence. Our recent finding that cocaine withdrawal stress increases the AVP mRNA in the amygdala through opioid receptors, suggests a functional interaction between the opioidergic and AVPergic systems in the amygdala (Zhou et al, 2005).…”

Section: Discussionmentioning

confidence: 84%

Involvement of Arginine Vasopressin and V1b Receptor in Heroin Withdrawal and Heroin Seeking Precipitated by Stress and by Heroin

Zhou

Leri

Cummins

et al. 2007

Neuropsychopharmacol

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A previous study has shown that the stress responsive neurohormone arginine vasopressin (AVP) is activated in the amygdala during early withdrawal from cocaine. The present studies were undertaken to determine whether (1) AVP mRNA levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal (HPA) activity, would be altered during chronic intermittent escalating heroin administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10 days) spontaneous withdrawal; (2) foot shock stress would alter AVP mRNA levels in the amygdala or hypothalamus in rats withdrawn from heroin self-administration (7 days, 3 h/day, 0.05 mg/kg/ infusion); and (3) the selective V1b receptor antagonist SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter heroin seeking during tests of reinstatement induced by foot shock stress and by heroin primes (0.25 mg/kg), as well as HPA hormonal responses to foot shock. We found that AVP mRNA levels were increased during early spontaneous withdrawal in the amygdala only. This amygdalar AVP mRNA increase was no longer observed at the later stage of heroin withdrawal. Foot shock stress increased AVP mRNA levels in the amygdala of rats withdrawn from heroin self-administration, but not in heroin naïve rats. Behaviorally, SSR149415 dose-dependently attenuated foot shock-induced reinstatement and blocked heroin-induced reinstatement. Finally, SSR149415 blunted the HPA activation by foot shock. Together, these data in rats suggest that stress responsive AVP/V1b receptor systems (including the amygdala) may be critical components of the neural circuitry underlying the aversive emotional consequences of drug withdrawal, as well as the effect of negative emotional states on drug-seeking behavior.

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Section: Discussionmentioning

confidence: 84%

Involvement of Arginine Vasopressin and V1b Receptor in Heroin Withdrawal and Heroin Seeking Precipitated by Stress and by Heroin

Zhou

Leri

Cummins

et al. 2007

Neuropsychopharmacol

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“…(Table 1). Adult rats treated chronically with morphine or heroin resulted in μ receptor desensitization in the thalamus, periaqueductal gray, and brain stem [12,21,23]. One major difference with the previous studies was that desensitization in adults occurred after 12 days of morphine infusion and 34 to 40 days of heroin self-administration.…”

Section: Behavioral Expression Of Morphine Tolerance In P17 Ratsmentioning

confidence: 84%

Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine-tolerant infant rats

2007

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We have previously noted that the antinociceptive efficacy of morphine was significantly decreased in rat pups chronically infused with morphine from implanted osmotic minipumps. In this study, morphine was fully efficacious (i.e., 100% maximum possible effect, %MPE) in the 52 ºC tail-immersion test after a 72-h infusion from implanted saline-filled osmotic minipumps. However, administration of up to 1000 mg/kg s.c. morphine failed to elicit greater than a 27% MPE in rats infused with morphine at 2 mg/kg/h. Morphine was more efficacious when the water bath temperature was decreased to 49 ºC. Experiments were conducted to determine the mechanisms whereby chronic morphine administration leads to a decrease in antinociceptive efficacy. The kappa-opioid antagonist nor-binalorphimine completely blocked the antinociceptive effects of morphine in morphine-infused rat pups. The kappa agonist U50,488 elicited antinociception however, the requirement to use higher doses in morphine-than saline-infused rats indicates that kappa cross-tolerance was present. Thus, in tolerant rats the antinociceptive effects of high doses of morphine appear to be mediated through kappa-opioid receptors. The deltaopioid antagonist naltrindole was inactive in both treatment groups. DAMGO-stimulated [ 35 S]GTPγS and [ 3 H]naloxone binding reveal that the anatomical distribution of the mu-opioid receptor was consistent with that of the adult rat brain. In adult rats, the mu-opioid receptor is desensitized during morphine tolerance. However, desensitization was not evident in P17 rats based on the lack of significant decreases in [ 35 S]GTPγS binding. Furthermore, [ 3 H]naloxone binding indicated a lack of mu receptor downregulation in morphine-tolerant rat pups.

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“…]GTPgS autoradiography is a method that allows visualization and quantification of functional G-proteincoupled receptors in brain slices (Sim et al, 1997a). This method has been used, for example, to demonstrate changes in m-opioid receptor function after chronic morphine and heroin treatments (Sim et al, 1996b;Sim-Selley et al, 2000), decreases in cannabinoid receptor activation after repeated tetrahydrocannabinol (Sim et al, 1996a), and heterologous regulation of 5-HT 1A receptors (Valdez et al, 2002). In the current study, autoradiography of LSD-stimulated [ 35 S]GTPgS binding revealed a region-specific attenuation of the cell signaling capacity of 5-HT 2A receptors in rats chronically treated with LSD.…”

Section: Discussionmentioning

confidence: 99%

Behavioral Tolerance to Lysergic Acid Diethylamide is Associated with Reduced Serotonin-2A Receptor Signaling in Rat Cortex

Gresch

Smith

Barrett

et al. 2005

Neuropsychopharmacol

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Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 mg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 mg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 mg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated 125 I-LSD binding to 5-HT 2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT 2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance to the discriminative stimulus effects of LSD.

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Chronic Heroin Self-Administration Desensitizes μ Opioid Receptor-Activated G-Proteins in Specific Regions of Rat Brain

Cited by 153 publications

References 40 publications

Involvement of Arginine Vasopressin and V1b Receptor in Heroin Withdrawal and Heroin Seeking Precipitated by Stress and by Heroin

Involvement of Arginine Vasopressin and V1b Receptor in Heroin Withdrawal and Heroin Seeking Precipitated by Stress and by Heroin

Role of kappa and delta opioid receptors in mediating morphine-induced antinociception in morphine-tolerant infant rats

Behavioral Tolerance to Lysergic Acid Diethylamide is Associated with Reduced Serotonin-2A Receptor Signaling in Rat Cortex

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