Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression

Camarini, Rosana; Pautassi, Ricardo Marcos

doi:10.1016/j.brainresbull.2016.04.006

Cited by 53 publications

(45 citation statements)

References 311 publications

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“…Additionally, females treated with 5 mg/kg ketamine displayed an aversion at this dose, while also developing sensitization. Interestingly, it has been demonstrated with other drugs such as ethanol that conditioned place aversion (CPA) occurs in naïve-drinking male rats, despite the well-established induction of ethanol sensitization (Rustay et al , 2001; Tzschentke, 2007; Camarini and Pautassi, 2016). Also, the presence of both estradiol and progesterone have been shown to enhance cocaine CPP in ovariectomized (OVX) female rats (Segarra et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

et al. 2017

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Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.

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Section: Discussionmentioning

confidence: 99%

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

et al. 2017

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“…Other possibility is that repeated AMPH treatment favors the development of behavioral sensitization, which in turn is associated with greater risk for exacerbated ethanol seeking and intake (Camarini & Pautassi, 2016). Support for this hypothesis comes from a study in which psychostimulant users exhibited heightened heart rate response to an ethanol challenge (Brunelle, Barrett, & Pihl, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The sensitization induced by drugs of abuse, which is thought to reflect the transition from a nonaddicted to an addicted state, can occur at many levels, yet it has been most often analyzed by assessing the progressive increase in drug‐induced motor stimulation that results from repeated drug exposure (Camarini & Pautassi, 2016). It should be noted, however, that some have suggested that a low level of response to the stimulant effects of ethanol or psychostimulants can also be a risk factor for drug addiction disorders.…”

Section: Introductionmentioning

confidence: 99%

“…In this protocol, animals are given repeated treatment with a drug or its vehicle followed by a challenge test, in which all receive a lower dose of the drug than that used during training. The rationale is that the acute effect of the lower dose will be higher (i.e., sensitized) in those with chronic exposure to the drug than in drug‐naïve controls (Camarini & Pautassi, 2016; Kuczenski & Segal, 2001). …”

Section: Introductionmentioning

confidence: 99%

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Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

et al. 2018

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IntroductionThere has been an increasing interest in analyzing the interactions between stimulants and ethanol during childhood and adolescence. Stimulants are used to treat attention‐deficit hyperactivity disorder (ADHD) in these developmental stages, during which ethanol initiation and escalation often occur.MethodsThis study assessed the effects of repeated d‐amphetamine (AMPH) or methylphenidate (MPH) treatment during adolescence [male and female Wistar rats, between postnatal day (PD) 28 to PD34, approximately] on the initiation of ethanol intake during a later section of adolescence (PD35 to PD40).ResultsAmphetamine and MPH exerted reliable acute motor stimulant effects, but there was no indication of sensitized motor or anxiety responses. MPH did not affect dopamine (DA) levels, whereas AMPH significantly reduced insular levels of DA in both sexes and norepinephrine levels in females only. Repeated treatment with AMPH, but not with MPH, enhanced ethanol intake during late adolescence in male, but not in female, rats.ConclusionA short treatment with AMPH during adolescence significantly altered DA levels in the insula, both in male and females, and significantly enhanced ethanol intake in males. The present results suggest that, in adolescent males, a very brief history of AMPH exposure can facilitate the initiation of ethanol intake.

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“…This might be because of the ontogeny of the dopaminergic system with an inverted U-shaped format in brain regions involved in motivation and rewarding (McCutcheon and Marinelli, 2009). Functional characteristics of the dopaminergic system during development have been implicated in distinct patterns of behavioral response to drugs between younger and older animals, such as sensitization and/or consumption (Doremus et al, 2005; Frantz et al, 2007; Camarini et al, 2008; Faria et al, 2008; Valzachi et al, 2013; Camarini and Pautassi, 2016). …”

Section: Discussionmentioning

confidence: 99%

Ethanol Sensitization during Adolescence or Adulthood Induces Different Patterns of Ethanol Consumption without Affecting Ethanol Metabolism

Carrara-Nascimento

Hoffmann

Contó

et al. 2017

Front. Behav. Neurosci.

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In previous study, we demonstrated that ethanol preexposure may increase ethanol consumption in both adolescent and adult mice, in a two-bottle choice model. We now questioned if ethanol exposure during adolescence results in changes of consumption pattern using a three-bottle choice procedure, considering drinking-in-the-dark and alcohol deprivation effect as strategies for ethanol consumption escalation. We also analyzed aldehyde dehydrogenase (ALDH) activity as a measurement of ethanol metabolism. Adolescent and adult Swiss mice were treated with saline (SAL) or 2.0 g/kg ethanol (EtOH) during 15 days (groups: Adolescent-SAL, Adolescent-EtOH, Adult-SAL and Adult-EtOH). Five days after the last injection, mice were exposed to the three-bottle choice protocol using sucrose fading procedure (4% + sucrose vs. 8%–15% ethanol + sucrose vs. water + sucrose) for 2 h during the dark phase. Sucrose was faded out from 8% to 0%. The protocol was composed of a 6-week acquisition period, followed by four withdrawals and reexposures. Both adolescent and adult mice exhibited ethanol behavioral sensitization, although the magnitude of sensitization in adolescents was lower than in adults. Adolescent-EtOH displayed an escalation of 4% ethanol consumption during acquisition that was not observed in Adult-EtOH. Moreover, Adult-EtOH consumed less 4% ethanol throughout all the experiment and less 15% ethanol in the last reexposure period than Adolescent-EtOH. ALDH activity varied with age, in which older mice showed higher ALDH than younger ones. Ethanol pretreatment or the pattern of consumption did not have influence on ALDH activity. Our data suggest that ethanol pretreatment during adolescence but not adulthood may influence the pattern of ethanol consumption toward an escalation in ethanol consumption at low dose, without exerting an impact on ALDH activity.

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Behavioral sensitization to ethanol: Neural basis and factors that influence its acquisition and expression

Cited by 53 publications

References 311 publications

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats

Amphetamine, but not methylphenidate, increases ethanol intake in adolescent male, but not in female, rats

Ethanol Sensitization during Adolescence or Adulthood Induces Different Patterns of Ethanol Consumption without Affecting Ethanol Metabolism

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