Suppression of Ethanol Responding by Centrally Administered CTOP and Naltrindole in AA and Wistar Rats

Hyytiä, Petri; Kiianmaa, Kalervo

doi:10.1111/j.1530-0277.2001.tb02123.x

Cited by 132 publications

(105 citation statements)

References 40 publications

(41 reference statements)

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“…It seems unlikely that the lack of effect of naltrindole on ethanol sensitization could be explained by an insufficient dose, as we used doses similar or even higher than those reported to be effective in reducing, for instance, voluntary ethanol consumption or the conditioned reinstatement of ethanol-seeking behavior (Ciccocioppo et al, 2002;Hyytia and Kiianmaa, 2001;Kim et al, 2000). The current results suggest, therefore, that the neural adaptations responsible for the development of sensitization to ethanol require the activation of mu but not delta opioid receptors.…”

Section: Discussionmentioning

confidence: 64%

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

Pastor

Aragón

2005

Neuropsychopharmacol

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Nonspecific blockade of opioid receptors has been found to prevent development of behavioral sensitization to ethanol. Whether this effect is achieved through a specific opioid receptor subtype, however, is not clear. The present study investigated, for the first time, the role of specific opioid receptor subtypes in the development of ethanol-(2.5 g/kg/day; six sessions) induced locomotor sensitization in mice. We confirmed previous results showing that the nonspecific antagonism of opioid receptors (naltrexone; 0-2 mg/kg) prevented the development of behavioral sensitization to ethanol, an effect attained at doses presumed to occupy only mu opioid receptors. This was confirmed by using the selective mu opioid receptor antagonist CTOP (0-1.5 mg/kg), which also blocked sensitization to ethanol. The selective delta receptor antagonist, naltrindole (0-10 mg/kg), however, did not alter sensitization. We further assessed the role of mu opioid receptors in sensitization to ethanol by exploring the involvement of mu 1 , mu 1 + 2 , and mu 3 opioid receptor subtypes. Results of these experiments revealed that the blockade of mu 1 (naloxonazine; 0-30 mg/kg) or mu 3 opioid receptors (3-methoxynaltrexone; 0-6 mg/kg) did not prevent locomotor sensitization to ethanol. Using naloxonazine under treatment conditions that block mu 1 + 2 opioid receptor subtypes we observed a retarded sensitization. The present data suggest that the concurrent inactivation of all mu opioid receptor subtypes may be required to prevent the neural adaptations underlying the development of behavioral sensitization to ethanol. In addition, these results support previous data suggesting a putative role for the mu opioid receptor endogenous ligand, b-endorphin, and the hypothalamic arcuate nucleus in ethanol sensitization.

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Section: Discussionmentioning

confidence: 64%

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

Pastor

Aragón

2005

Neuropsychopharmacol

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“…Nonspecific opioid receptor antagonists, such as naloxone and naltrexone, reduce ethanol intake in rats (Coonfield et al, 2002;Froehlich et al, 1990) and mice (Middaugh et al, 1999). Naltrindole, a selective δ-opioid receptor antagonist, was found to suppress the ethanol self-administration in a similar manner in AA and Wistar rats (Hyytia & Kiianmaa, 2001). In contrast, the activation of κ-opioid receptors by a selective agonist, U50,488H, dosedependently decreased ethanol intake in rats (Lindholm et al, 2001).…”

Section: Introductionmentioning

confidence: 98%

Reduced alcohol consumption in mice lacking preprodynorphin

Blednov

Walker

Martinez

et al. 2006

Alcohol

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Many studies suggest a role for endogenous opioid peptides and their receptors in regulation of ethanol intake. It is commonly accepted that the κ-opioid receptors and their endogenous ligands, dynorphins, produce a dysphoric state and therefore may be responsible for avoidance of alcohol. We used mutant mice lacking preprodynorphin in a variety of behavioral tests of alcohol actions. Null mutant female, but not male, mice showed significantly lower preference for alcohol and consumed lower amounts of alcohol in a two-bottle choice test as compared with wild-type littermates. In the same test, knockout mice of both sexes showed a strong reduction of preference for saccharin compared to control mice. In contrast, under conditions of limited (4 hours) access (light phase of the light/dark cycle), null mutant mice did not show any differences in consumption of saccharin but they showed significantly reduced intake of sucrose. To determine the possible cause for reduction of ethanol preference and intake, we studied other ethanol-related behaviors in mice lacking the preprodynorphin gene. There were no differences between null mutant and wild type mice in ethanol-induced loss of righting reflex, acute ethanol withdrawal, ethanol-induced conditioned place preference or conditioned taste aversion to ethanol. These results indicate that deletion of preprodynorphin leads to substantial reduction of alcohol intake in female mice, and suggest thath this is caused by decreased orosensory reward of alcohol (sweet taste and/or palatability).

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“…Further, naltrexone (NAL) decreases operant responding for ethanol in rats, and decreases ethanol intake in rodents and humans (O'Malley et al, 2000;Hyytia and Sinclair, 1993;Froehlich et al, 1990). Selective receptor antagonists for both m- (Hyytia and Kiianmaa, 2001) and d-opioid receptors (Krishnan-Sarin et al, 1995) are also efficacious in decreasing ethanol intake.…”

Section: Introductionmentioning

confidence: 99%

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

Burghardt

Wilson

2005

Neuropsychopharmacol

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The amygdala is involved in behavioral and physiological responses to fear, and the anxiolytic properties of several drugs are localized to this region. Activation of endogenous opioid systems is known to occur in response to stress and a growing body of literature suggests that opioid systems regulate the properties of anxiolytic drugs. These experiments sought to elucidate the role of opioid receptors in the central (CeA) and basolateral (BLA) nuclei of the amygdala in regulating the anxiolytic properties of ethanol and diazepam. Male rats fitted with cannula received bilateral microinjections of the nonselective opioid receptor antagonist naltrexone (NAL) immediately followed by systemic delivery of either ethanol (1 g/kg) or diazepam (2 mg/kg) in the elevated plus maze. Both diazepam and ethanol decreased anxiety-like behavior. Delivery of NAL into the CeA blocked the anxiolytic properties of diazepam. Delivery of NAL into the BLA slightly increased open arm avoidance, but had no effect on the anxiolytic properties of diazepam. Microinjection of NAL into either nucleus failed to block the effects of ethanol. These results were specific to the anxiolytic properties of diazepam, since baseline behaviors were unaffected by microinjection of NAL. Microinjection of lidocaine produced results distinct from NAL and failed to block the anxiolytic actions of diazepam. These studies indicate distinct roles for opioid receptor systems in the CeA and BLA in regulating the anxiolytic properties of diazepam in the elevated plus maze. Further, opioid receptor systems in the CeA and BLA do not regulate the anxiolytic properties of ethanol in this test.

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Suppression of Ethanol Responding by Centrally Administered CTOP and Naltrindole in AA and Wistar Rats

Cited by 132 publications

References 40 publications

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

The Role of Opioid Receptor Subtypes in the Development of Behavioral Sensitization to Ethanol

Reduced alcohol consumption in mice lacking preprodynorphin

Microinjection of Naltrexone into the Central, but not the Basolateral, Amygdala Blocks the Anxiolytic Effects of Diazepam in the Plus Maze

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