Reversal-Specific Learning Impairments After a Binge Regimen of Methamphetamine in Rats: Possible Involvement of Striatal Dopamine

Izquierdo, Alicia; Belcher, Annabelle M.; Scott, Lori N.; Cazares, Victor A.; Chen, Jack; O’Dell, Steven J.; Malvaez, Melissa; Wu, Tiffany; Marshall, John F.

doi:10.1038/npp.2009.155

Cited by 89 publications

(120 citation statements)

References 72 publications

(90 reference statements)

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“…DAT heterozygotes and GBR 12909-treated mice were able to learn, but learning was significantly slower (more trials to criterion) than in WT and control mice and they committed more commission errors to the criterion in the Rev stage (and IDS) than WT and control mice. Difficulties in the reversal task have been previously shown in DAT+/− mice when tested in the H-maze (Del'Guidice et al 2014) and have also been produced by reductions in striatal dopamine transporters evoked by methamphetamine administration (Izquierdo et al 2010). Treatment of mice with the potent and selective DAT inhibitor GBR 12909 (van der Zee et al 1980, Heikkila and Manzino 1984, Andersen 1989) would be expected initially to reduce DAT activity, but subsequently upon drug withdrawal, induce a rebound DAT over-expression, as has been previously postulated (Hewitt et al 2005(Hewitt et al , 2009).…”

Section: Discussionmentioning

confidence: 99%

Potential role of dopamine transporter in behavioral flexibility

Cybulska-Kłosowicz¹,

Dąbrowska²,

Niedzielec³

et al. 2017

Acta Neurobiologiae Experimentalis

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Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes. Here we used a gene knockout mouse model to investigate the role of DAT in the performance on the Attentional Set-Shifting Task (ASST) stages dependent upon the OFC and the DMS. Additionally, behavior of mice after repeated administration of selective DAT inhibitor, GBR 12909, was examined.The animals were treated with the inhibitor to elicit a compensatory DAT up-regulation following withdrawal. Learning was slower and the number of errors during reversal learning and intra-dimensional shift stages was higher in DAT+/− mutant mice than in WT mice. GBR 12909-treated mice had deficits in reversal stages of the ASST. Neuronal activation in the OFC and DMS during the ASST was examined with early growth response proteins 1 and 2 (egr-1, egr-2) immunohistochemistry. Density of egr-2 labeled cells in the OFC was lower in mutant mice than in wild-types during reversal learning and the expression of the egr-1 was lower in mutant mice in the OFC and DMS during reversal and intra-dimensional shift stages. Mice with decreased DAT levels displayed behavioral difficulties that were accompanied by a lower task-induced activation of neurons in brain regions involved in the reversal learning. Altogether, these data indicate the role of the DAT in the behavioral flexibility.

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Section: Discussionmentioning

confidence: 99%

Potential role of dopamine transporter in behavioral flexibility

Cybulska-Kłosowicz¹,

Dąbrowska²,

Niedzielec³

et al. 2017

Acta Neurobiologiae Experimentalis

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“…Studies on rodent models of Meth addiction have recently focused on drug bingeing paradigms to investigate Meth-induced behavioral impairments (Belcher et al, 2008;Izquierdo et al, 2010;O'Dell et al, 2011), neuroplastic changes (Brennan et al, 2010), and neurotoxicity (Moszczynska et al, 1998;Kuczenski et al, 2007;Graham et al, 2008). The main objective of these studies was to achieve plasma drug levels in the rat close to those found in human Meth addicts.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

Frohmader¹,

Lehman²,

Laviolette³

et al. 2011

J. Neurosci.

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Methamphetamine (Meth) users report having heightened sexual pleasure, numerous sexual partners, and engaging in unprotected sex due to loss of inhibitory control. This compulsive sexual behavior contributes to increased prevalence of sexually transmitted infections, but the neural basis for this is unknown. We previously established a paradigm for compulsive sexual behavior in male rats in which visceral illness induced by lithium chloride was paired with sexual behavior (

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“…When assessed at least 1 week after MA administration, rats and mice that are administered large, binge doses of MA (X4 mg/kg per dose, often multiple times per day) exhibit deficits in several cognitive domains, including object recognition memory (Belcher et al, 2005;Siegel et al, 2010), odor recognition memory (O'Dell et al, 2011), spatial learning (Acevedo et al, 2007;Vorhees et al, 2009), sequential learning (Chapman et al, 2001;Daberkow et al, 2005), path integration learning (Herring et al, 2008), working memory (Mizoguchi et al, 2011), effort discounting (similar to delay discounting) (Kosheleff et al, 2012), and reversal learning (Izquierdo et al, 2010).…”

Section: Animals Exposed To Ma Will Show Cognitive Decline Particulamentioning

confidence: 99%

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

Dean

Groman

Morales

et al. 2012

Neuropsychopharmacol

209

127

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Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) crosssectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual.

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Reversal-Specific Learning Impairments After a Binge Regimen of Methamphetamine in Rats: Possible Involvement of Striatal Dopamine

Cited by 89 publications

References 72 publications

Potential role of dopamine transporter in behavioral flexibility

Potential role of dopamine transporter in behavioral flexibility

Concurrent Exposure to Methamphetamine and Sexual Behavior Enhances Subsequent Drug Reward and Causes Compulsive Sexual Behavior in Male Rats

An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

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