Importance of delta opioid receptors in maintaining high alcohol drinking

Froehlich, Janice C.; Zweifel, M.; Harts, J.; Lumeng, Lawrence; Li, T. K.

doi:10.1007/bf02244246

Cited by 208 publications

(112 citation statements)

References 34 publications

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“…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]. It may be that ET females are more sensitive to the acute effects of ethanol and may show an increase in intake of ethanol compared to males.…”

Section: Discussionmentioning

confidence: 99%

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

Lugo¹,

Wilson²,

Kelly³

2006

Neurotoxicology and Teratology

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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.

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Section: Discussionmentioning

confidence: 99%

“…Ethanol exposure significantly increased the basal met-enkephalin levels in the ET females compared to the IC females. The sample sizes for NTC males, NTC females, IC males, IC females, ET males, and ET females were n = 7, 8,8,8,8,8, respectively. The asterisk indicates a significant difference.…”

Section: Discussionmentioning

confidence: 99%

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

Lugo¹,

Wilson²,

Kelly³

2006

Neurotoxicology and Teratology

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“…These lines of evidence support the hypothesis that reduction of A2AR-CREB activity in the DMS is critical to establish the reinforcing properties in the initial stages of habit formation. In addition, many alcohol preferring rodents exhibit lower enkephalin expression in the midbrain in comparison to non-preferring control animals and also have increased sensitivity to opioid alterations by ethanol treatment (Froehlich et al, 1991;Li et al, 1998;Mendez and Morales-Mulia, 2006;Ng et al, 1996). Thus, decreased CREB activity, possibly downstream of A2AR in the DMS, also promotes excessive ethanol seeking, which is governed by positive reinforcement and sensitivity to goal-directed responses during the extinction stage.…”

Section: A2ar Inhibition In the Dms And Goal Directed Drinkingmentioning

confidence: 99%

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

Nam

Bruner

Choi

2013

Molecules and Cells

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Adenosine signaling has been implicated in the pathophysiology of alcohol use disorders and other psychiatric disorders such as anxiety and depression. Numerous studies have indicated a role for A1 receptors (A1R) in acute ethanol-induced motor incoordination, while A2A receptors (A2AR) mainly regulate the rewarding effect of ethanol in mice. Recent findings have demonstrated that dampened A2AR-mediated signaling in the dorsomedial striatum (DMS) promotes ethanol-seeking behaviors. Moreover, decreased A2AR function is associated with decreased CREB activity in the DMS, which enhances goal-oriented behaviors and contributes to excessive ethanol drinking in mice. Interestingly, caffeine, the most commonly used psychoactive substance, is known to inhibit both the A1R and A2AR. This dampened adenosine receptor function may mask some of the acute intoxicating effects of ethanol. Furthermore, based on the fact that A2AR activity plays a role in goal-directed behavior, caffeine may also promote ethanol-seeking behavior. The A2AR is enriched in the striatum and exclusively expressed in striatopallidal neurons, which may be responsible for the regulation of inhibitory behavioral control over drug rewarding processes through the indirect pathway of the basal ganglia circuit. Furthermore, the antagonistic interactions between adenosine and dopamine receptors in the striatum also play an integral role in alcoholism and addiction-related disorders. This review focuses on regulation of adenosine signaling in striatal circuits and the possible implication of caffeine in goal-directed behaviors and addiction.

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“…Pharmacological blockage of the endogenous opioid system by m-and d-receptor antagonists prevents ethanol from activating the dopamine system and reduces ethanol craving and consumption. [20][21][22] Thus, m-and d-receptor antagonists can be useful in the treatment of AD. Naltrexone, one of only three approved pharmacotherapies for AD and OD, is thought to exert its actions primarily by blocking the m-receptor.…”

Section: Introductionmentioning

confidence: 99%

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

et al. 2007

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Eleven single-nucleotide polymorphisms (SNPs) spanning OPRD1 were examined in 1063 European Americans (EAs) (620 cases with substance dependence (SD), including 557 with alcohol dependence (AD), 225 with cocaine dependence (CD) and 111 with opioid dependence (OD), and 443 controls). Nominally significant associations (P < 0.05) of five SNPs with SD were observed; only the association of the non-synonymous variant G80T with OD remained significant after correction for multiple testing using SNPSpD. Haplotype analyses with six tag SNPs indicated that a specific haplotype GCAACT, which harbors G80T G-allele and C921T C-allele, was significantly associated with AD (v 2 = 14.82, degrees of freedom (d.f.) = 1, P < 0.001), CD (v 2 = 9.19, d.f. = 1, P = 0.002) and OD (v 2 = 20.68, d.f. = 1, P < 0.001). Logistic regression analyses, with sex and age being considered, demonstrated that this haplotype had a risk effect on AD (P = 0.03, b = 1.86, odds ratio (OR) = 6.43) and especially on OD (P < 0.001, b = 3.92, OR = 50.57). Moreover, seven SNPs covering OPRK1 were examined in the majority of the above subjects (390 cases, including 327 AD, 177 CD and 97 OD subjects, and 358 controls). Although no significant differences in allele, genotype or haplotype frequency distributions were seen between cases and controls, a specific OPRK1 haplotype, GGCTTCT, was significantly associated with AD (v 2 = 8.12, d.f. = 1, P = 0.004). Logistic regression analyses also revealed its risk effect on AD (P = 0.009, b = 1.06, OR = 2.90). Population stratification artifact was not observed in the sample. Taken together, our findings supported a positive association between OPRD1 variants and SD, and a positive haplotypic association between OPRK1 and AD in EAs.

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Importance of delta opioid receptors in maintaining high alcohol drinking

Cited by 208 publications

References 34 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

Adenosine Signaling in Striatal Circuits and Alcohol Use Disorders

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

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