The negative effects of alcohol hangover on high-anxiety phenotype rats are influenced by the glutamate receptors of the dorsal midbrain

Leite, Luan de Souza; Nobre, Manoel Jorge

doi:10.1016/j.neuroscience.2012.04.009

Cited by 19 publications

(13 citation statements)

References 65 publications

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“…Although adolescents are less sensitive to the negative aspects of alcohol use (Spear & Varlinskaya, 2005), adolescents have significant and persistent anxiety produced by alcohol withdrawal. Since withdrawal-related anxiety is associated with relapse (Fox et al, 2007; Leite & Nobre, 2012; Roberts et al, 1999; Willinger et al, 2002), the main implication of our finding is that both adolescents and adults experience persistent withdrawal-induced increases in anxiety which may underlie treatment difficulties across the lifespan.…”

Section: Discussionmentioning

confidence: 74%

“…Given that withdrawal-related anxiety is associated with relapse (Fox et al, 2007; Leite & Nobre, 2012; Roberts et al, 1999; Willinger et al, 2002), one of the primary goals of this study is to assess the persistence of anxiety-like behavior associated with CIE exposure and withdrawal in adolescent and adult rats. Additionally dependence, tolerance, and withdrawal symptoms in the adult rat are marked by increased function of NMDA receptors (Grant et al, 1990; Krystal et al, 1998; Leite & Nobre, 2012; Sanna et al, 1993) and attenuated function of GABA A receptors (Grobin et al,.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally dependence, tolerance, and withdrawal symptoms in the adult rat are marked by increased function of NMDA receptors (Grant et al, 1990; Krystal et al, 1998; Leite & Nobre, 2012; Sanna et al, 1993) and attenuated function of GABA A receptors (Grobin et al,. 1998; Kang et al, 1998; Kang et al, 1996; Morrow, 1995), which coincide with altered receptor subunit expression (Grobin et al, 1998; Kang et al, 1996; Morrow, 1995; Pian et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Intermittent Ethanol Exposure Produces Persistent Anxiety in Adolescent and Adult Rats

Skike

Diaz-Granados

Matthews

2015

Alcoholism Clin & Exp Res

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Background Ethanol dependence and tolerance in the adult are marked by increased function of NMDA receptors and decreased function of GABAA receptors that coincides with altered receptor subunit expression in specific brain regions. Adolescents often use ethanol at levels greater than adults, yet the receptor subunit expression profiles following chronic intermittent ethanol (CIE) exposure in adolescents are not known. Persistent age-dependent changes in receptor subunit alterations coupled with withdrawal-related anxiety may help explain the increase in alcohol abuse following adolescent experimentation with the drug. Methods Adolescent and adult rats received 10 intraperitoneal administrations of 4.0 g/kg ethanol or saline every 48 hours. At either 24 hours or 12 days after the final exposure, anxiety-like behavior was assessed on the elevated plus maze and tissue was collected. Western blotting was used to assess changes in selected NMDA and GABAA receptor subunits in whole cortex and bilateral hippocampus. Results CIE exposure yields a persistent increase in anxiety-like behavior in both age groups. However, selected NMDA and GABAA receptor subunits were not differentially altered by this CIE exposure paradigm in adolescents or adults. Conclusions CIE exposure produced persistent anxiety-like behavior, which has important implications for alcohol cessation. Given the reported behavioral and neuropeptide expression changes in response to this dose of ethanol, it is important for future work to consider the circumstances under which these measures are altered by ethanol exposure.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic Intermittent Ethanol Exposure Produces Persistent Anxiety in Adolescent and Adult Rats

Skike

Diaz-Granados

Matthews

2015

Alcoholism Clin & Exp Res

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“…The DYN/KOR system also modulates dopaminergic neurons projecting to the prefrontal cortex (Margolis et al, 2006). The KOR agonist, U69593, leads to a decrease in GABA and glutamate in the Acb (Hjelmstad and Fields, 2003); both neurotransmitters that are important in addiction (Walker and Koob, 2007;Walker and Ettenberg, 2001;Ezequiel and Nobre, 2012). Activation of the p38 mitogen-activated protein kinase system via stress-induced negative affect is KOR dependent , and p38 activation also regulates the serotonergic system (Samuvel et al, 2005), which has recently been shown to innervate the Acb and is susceptible to KOR regulation .…”

Section: Discussionmentioning

confidence: 99%

Affective Cue-Induced Escalation of Alcohol Self-Administration and Increased 22-kHz Ultrasonic Vocalizations during Alcohol Withdrawal: Role of Kappa-Opioid Receptors

Berger¹,

Williams²,

McGinnis³

et al. 2012

Neuropsychopharmacol

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Negative affect promotes dysregulated alcohol consumption in non-dependent and alcohol-dependent animals, and cues associated with negative affective states induce withdrawal-like symptoms in rats. This study was designed to test the hypotheses that: (1) the kappaopioid receptor (KOR) system mediates phenotypes related to alcohol withdrawal and withdrawal-like negative affective states and (2) cues associated with negative affective states would result in dysregulated alcohol consumption when subsequently presented alone. To accomplish these goals, intracerebroventricular infusion of the KOR antagonist nor-binaltorphimine (nor-BNI) was assessed for the ability to attenuate the increase in 22-kHz ultrasonic vocalizations (USVs) associated with alcohol withdrawal and KOR activation in adult male wistar rats. Furthermore, cues associated with a KOR agonist-induced negative affective state were assessed for the ability to dysregulate alcohol consumption and the efficacy of intracerebroventricular KOR antagonism to reduce such dysregulation was evaluated. KOR antagonism blocked the increased number of 22-kHz USVs observed during acute alcohol withdrawal and a KOR agonist (U50,488) resulted in a nor-BNI reversible increase in 22-kHz USVs (mimicking an alcohol-dependent state). Additionally, cues associated with negative affective states resulted in escalated alcohol self-administration, an effect that was nor-BNI sensitive. Taken together, this study implicates negative affective states induced by both alcohol withdrawal and conditioned stimuli as being produced, in part, by activity of the DYN/KOR system.

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“…This analysis was also performed in five animals of each of the ISO groups. The BAL measure was carried out immediately after the end of the 2 h free-drinking session to measure the blood-alcohol decay during the next 6 h of alcohol withdrawal, as previously described (Ezequiel Leite and Nobre, 2012;Morse et al, 2000;Schulteis and Liu, 2006). During this period, water was the only fluid available.…”

Section: Blood-alcohol Levels (Bal) Analysismentioning

confidence: 99%

Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake

Nobre

2016

Intl J of Devlp Neuroscience

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Exposure to stress and prolonged exposure to alcohol leads to neuronal damages in several brain regions, being the medial prefrontal cortex (mPFC) one of the most affected. These changes presumably reduce the ability of the organism to cope with these stimuli and may underlie a series of maladaptive behaviours among which include drug addiction and withdrawal. Drug-addicted individuals show a pattern of behavior similar to patients with lesions of the mPFC. This impairment in the decision-making could be one of the mechanisms responsible for the transition from the casual to compulsive drug use. The environmental enrichment (EE) has a protective effect on the neural and cognitive impairments induced by psychoactive drugs, including ethyl alcohol. The present study aims to determine the influence of withdrawal from intermittent long-term alcohol exposure on alcohol preference, emotional reactivity and neural aspects of early isolated or grouped reared rats kept under standard or complex environments and the influence of social isolation on these measures, as well. Our results point out new insights on this matter showing that the EE can attenuate the adverse effects of withdrawal and social isolation on rat's behavior. This effect is probably due to its protective action on the mPFC integrity, including the cingulate area 1 (Cg1), and the prelimbic (PrL) and infralimbic cortex (IL), what could account for the absence of changes in the emotional reactivity in EE alcohol withdrawal rats. We argue that morphological changes at these cortical levels can afford the emotional, cognitive and behavioural dysregulations verified following withdrawal from chronic alcohol intake.

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The negative effects of alcohol hangover on high-anxiety phenotype rats are influenced by the glutamate receptors of the dorsal midbrain

Cited by 19 publications

References 65 publications

Chronic Intermittent Ethanol Exposure Produces Persistent Anxiety in Adolescent and Adult Rats

Chronic Intermittent Ethanol Exposure Produces Persistent Anxiety in Adolescent and Adult Rats

Affective Cue-Induced Escalation of Alcohol Self-Administration and Increased 22-kHz Ultrasonic Vocalizations during Alcohol Withdrawal: Role of Kappa-Opioid Receptors

Environmental enrichment may protect against neural and behavioural damage caused by withdrawal from chronic alcohol intake

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