A microdialysis profile of ?-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration

Marinelli, Peter W.; Quirion, Rémi; Gianoulakis, Christina

doi:10.1007/s00213-003-1490-2

Cited by 122 publications

(134 citation statements)

References 51 publications

Supporting

Mentioning

120

Contrasting

Unclassified

Order By: Relevance

“…The sex-specific change in met-enkephalin levels may also explain why only ethanol-exposed female mice are less sensitive to the low-dose stimulant effect of ethanol [1]. Acute ethanol exposure increases the opioid peptide betaendorphin in NA [21,26]. Additionally, enkephalinase inhibitor, which potentiates the action of endogenous enkephalins, increases alcohol intake [8], while an opioid antagonist administered into the NA decreases the animal's response to alcohol [12].…”

Section: Discussionmentioning

confidence: 99%

Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

Lugo¹,

Wilson²,

Kelly³

2006

Neurotoxicology and Teratology

View full text Add to dashboard Cite

This study used a rat model of Fetal Alcohol Syndrome to investigate whether combined prenatal and postnatal ethanol exposure affects met-enkephalin levels in the brains of male and female Long-Evans adult rats. Intragastric ethanol was administered to a group of rats (ET) from gestational day (GD) 1 through 22 and from postnatal day (PD) 2 through 10. The control groups consisted of a nontreated control group (NTC) and an intubated control group (IC) that received the intragastric intubation procedure but no exposure to ethanol. We measured met-enkephalin levels in the prefrontal cortex, nucleus accumbens, hypothalamus, central and basolateral nucleus of amygdala and ventral tegmental area. Met-enkephalin levels in the hypothalamus of male and female ET animals were significantly higher than those in either the NTC or IC animals. Metenkephalin levels in the central nucleus of the amygdala of male and female ET animals were significantly lower than the levels in the NTC animals. Met-enkephalin levels in the nucleus accumbens of ET females were significantly greater than those in the IC females. These results demonstrate that the combination of prenatal and postnatal ethanol exposure affects basal metenkephalin levels in specific regions in a sex-specific manner. These changes in met-enkephalin levels may explain how early ethanol exposure affects opioid-regulated behaviors such as social play, sexual behavior, and other social behaviors.

show abstract

Section: Discussionmentioning

confidence: 99%

Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

Lugo¹,

Wilson²,

Kelly³

2006

Neurotoxicology and Teratology

View full text Add to dashboard Cite

show abstract

“…To our understanding, however, the most convincing proposal to comprehend the neural mechanism by which these receptors participate in ethanol sensitization may be related to the actions of the mu opioid receptor endogenous ligand, b-endorphin. Ethanol administration produces an increase in b-endorphin release, as measured by in vivo microdialysis in the NAcb (Olive et al, 2001;Marinelli et al, 2003). Also, acute administration of ethanol increased b-endorphin neurotransmission in the ventral tegmental area (VTA) (Rasmussen et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

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

Pastor

Aragón

2005

Neuropsychopharmacol

View full text Add to dashboard Cite

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.

show abstract

“…These include alterations in the function of the cholinergic, dopaminergic, g-aminobutyric acid, glutamatergic, opioidergic, and serotonergic neurotransmitter systems (for review see Eckardt et al, 1998). In the case of the endogenous opioid system and its receptor subtypes (m, d, kFselective for the three main classes of endogenous opioids: b-endorphin, enkephalins, and dynorphins, respectively), acute ethanol has been shown to stimulate the release of b-endorphin, enkephalins, and dynorphin in humans and rats (Gianoulakis et al, 1996;Marinelli et al, 2003Marinelli et al, , 2004Dai et al, 2005;Marinelli et al, 2005Marinelli et al, , 2006. Blockade of the receptors for these endogenous ligands by naltrexone and naloxone has been shown to reliably decrease ethanol consummatory behaviors (Gonzales and Weiss, 1998;Stromberg et al, 2001;Coonfield et al, 2002;Shoemaker et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Nalmefene is also classified as a general opioid receptor antagonist and is equipotent with naltrexone at the m-opioid receptor, but unlike naltrexone, has a higher affinity for the k and d receptors in rats (Michel et al, 1985) and the k receptor in humans (Bart et al, 2005). Therefore, even at low doses, nalmefene can be considered a 'true' general opioid receptor antagonist.Thus, based on the fact that naltrexone and nalmefene have dissociable binding profiles at the opioid receptors, and that previous research has shown acute changes in bendorphin, met-enkephalin, and dynorphin in response to ethanol (Gianoulakis et al, 1996;Marinelli et al, 2003Marinelli et al, , 2004Marinelli et al, , 2005Marinelli et al, , 2006Dai et al, 2005), the purpose of the present study was to compare ligands with mechanisms of action that are either m-opioid (ie naltrexone) or m-, d-, and k-opioid (ie nalmefene) receptor based for their ability to attenuate ethanol self-administration in nondependent and ethanoldependent rats during acute withdrawal. Furthermore, to test directly the contribution of dynorphin systems to the increased ethanol self-administration observed during acute withdrawal, central k-opioid receptors were selectively targeted for antagonism in nondependent and ethanoldependent rats.…”

mentioning

confidence: 99%

Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence

Walker

Koob

2007

Neuropsychopharmacol

365

376

View full text Add to dashboard Cite

The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (k)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are both opioid receptor ligands with comparable molecular weights and pharmacokinetic profiles, but differing specificity for the three opioid receptor subtypes at low doses, while nor-BNI is a selective k-opioid receptor antagonist. Dependence was induced in half the animals by subjecting them to a 4-week intermittent vapor exposure period in which animals were exposed to ethanol vapor for 14 h per day. Subsequent to dependence induction, nalmefene, naltrexone, and nor-BNI were tested for their ability to modulate self-administration of ethanol in vapor-exposed and control rats. The results indicated that both nalmefene and naltrexone induced a significant dose-dependent decrease in the number of lever presses for ethanol in both groups of animals. However, in ethanol-dependent animals, nalmefene was significantly more effective in suppressing ethanol intake than naltrexone. Nor-BNI selectively attenuated ethanol-dependent self-administration while leaving nondependent ethanol self-administration intact. Because naltrexone is primarily selective for the m-opioid receptor, and nalmefene is primarily selective for the m-and k-opioid receptor subtypes, the fact that nalmefene demonstrates more suppression in dependent animals suggests that opioid systems distinct from the m-regulated portion may be involved in the increased drinking seen during withdrawal in dependent animals. The results with nor-BNI confirm that k-opioid receptor antagonism selectively decreases dependence-induced ethanol self-administration, which supports the hypothesis that dynorphin/k-opioid systems are dysregulated in dependence and contribute to the increased drinking seen during acute withdrawal in dependent rats. INTRODUCTIONThe acute effects of ethanol have been shown to be both reinforcing and rewarding in animal models such as operant self-administration (Anderson and Thompson, 1974;Smith and Davis, 1974) and the conditioned place preference paradigm (Bozarth, 1990;Walker and Ettenberg, 2007). Ethanol produces its effects on the central nervous system via a variety of pharmacological mechanisms. These include alterations in the function of the cholinergic, dopaminergic, g-aminobutyric acid, glutamatergic, opioidergic, and serotonergic neurotransmitter systems (for review see Eckardt et al, 1998). In the case of the endogenous opioid system and its receptor subtypes (m, d, kFselective for the three main classes of endogenous opioids: b-endorphin, enkephalins, and dynorphins, respectively), acute ethanol has been shown to stimulate the release of b-endorphin...

show abstract

A microdialysis profile of ?-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration

Cited by 122 publications

References 51 publications

Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

Perinatal ethanol exposure alters met-enkephalin levels of male and female rats

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

Pharmacological Evidence for a Motivational Role of κ-Opioid Systems in Ethanol Dependence

Contact Info

Product

Resources

About