Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Kerstetter, Kerry A.; Kantak, Kathleen M.

doi:10.1007/s00213-007-0852-6

Cited by 39 publications

(56 citation statements)

References 52 publications

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“…The rewarding effects of cocaine do not appear to be enhanced in adolescent rats because the majority of studies do not show greater i.v. self administration [5,22,29,33,38]. We did not find differences in cocaine effects in nucleus accumbens, the region thought to mediate the rewarding effects of cocaine.…”

Section: Discussioncontrasting

confidence: 59%

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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The neural mechanisms responsible for the enhanced adolescent vulnerability for initiating drug abuse are unclear. We investigated whether age differences in dopamine neurotransmission could explain cocaine's enhanced psychomotor effects in the periadolescent rat. Electrical stimulation the medial forebrain bundle of anesthetized post-natal age 28 days (PN28) and PN65 rats elicited dopamine release in caudate nucleus and nucleus accumbens core before and after 15 mg/kg cocaine i.p. Extracellular dopamine concentrations were greater in PN65 than PN28 caudate following 20 and 60Hz stimulations and in the PN65 nucleus accumbens following 60Hz stimulations. Cocaine increased dopamine concentrations elicited by 20 Hz stimulations 3-fold in the adult, but almost 9-fold in periadolescent caudate. Dopamine release rate was lower in the periadolescent caudate although total dopamine clearance was similar to that of adults. The periadolescent caudate achieved adult levels of clearance by compensating for a lower V max with higher uptake affinity. Tighter regulation of extracellular dopamine by the higher uptake/release ratio in periadolescents led to greater increases after cocaine. In nucleus accumbens, dopamine release and V max were lower in periadolescents than adults, but uptake affinity and cocaine effects were similar. Immaturity of dopamine neurotransmission in dorsal striatum may underlie enhanced acute responses to psychostimulants in adolescent rats and suggests a mechanism for the greater vulnerability of adolescent humans to drug addiction.

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Section: Discussioncontrasting

confidence: 59%

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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“…For example, we observed similar rates of reinstatement among adolescent-and adult-onset groups when both context and cues were renewed simultaneously (Doherty and Frantz, 2012a). Also, extinction of a cocaineconditioned place preference occurred at the same rate in adolescent and adult rats when explicit extinction procedures were used (Brenhouse et al, 2010), and the age-dependent effects of cocaine self-administration on cognition vary by which brain region mediates the cognitive task (Kerstetter and Kantak, 2007;Harvey et al, 2009). These latter studies underscore the idea that different mechanisms may mediate extinction responding, context-induced reinstatement, and cue-induced reinstatement of drugseeking.…”

Section: Discussionmentioning

confidence: 54%

“…This result was independently replicated with cocaine-seeking (Anker and Carroll, 2010). It suggests that adolescent rats are less sensitive to some enduring drug effects, an interpretation supported by age differences in several cocaine-and nicotine-related behaviors (Balda et al, 2006;Kerstetter and Kantak, 2007;Shram et al, 2008), as well as fewer signs and symptoms of drug withdrawal among adolescent rodents compared with adults (Doherty and Frantz, 2012b); Doremus et al, 2003;O'Dell et al, 2006;Hodgson et al, 2009).…”

Section: Introductionmentioning

confidence: 68%

“…Cognitive impairment on an amydgala-dependent task after cocaine intake (but not an orbitofrontal cortex-dependent task) is also less severe in younger rats (Harvey et al, 2009;Kerstetter and Kantak, 2007). In further support of reduced enduring effects of heroin in adolescent rats compared with adults, somatic and locomotor signs of spontaneous withdrawal from repeated systemic heroin injections are attenuated, as are the effects of heroin on body weight and food intake (Doherty and Frantz, 2012b).…”

Section: Discussionmentioning

confidence: 90%

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A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

Doherty

Cooke

Frantz

2012

Neuropsychopharmacol

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Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir þ and Fos-ir À neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir þ neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin selfadministration.

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“…Alternatively, the cocaine administration procedures utilized in previous studies involved relatively limited access to drug. There is accumulating evidence that extended access to self-administered cocaine may produce a number of symptoms characteristic of addiction that are not seen following more limited drug access, including persistent cognitive deficits (Ahmed and Koob 1998;Paterson and Markou 2003;DerocheGamonet et al 2004;Vanderschuren and Everitt 2004;Ferrario et al 2005;George, et al 2007;Briand, et al 2008), although the influence of amount of access may be moderated by the use of higher doses (Burke, et al 2006;Calu, et al 2007;Kerstetter and Kantak 2007). Thus, the current experiment compared the effects of extended (6 hrs/day) or more limited (1 hr/day) access to cocaine on object recognition memory performance.…”

mentioning

confidence: 99%

Impaired object recognition following prolonged withdrawal from extended-access cocaine self-administration

2008

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Cocaine addicts have a number of cognitive deficits that persist following prolonged abstinence. These include impairments in executive functions dependent on the prefrontal cortex, as well as deficits on learning and memory tasks sensitive to hippocampal function. Recent preclinical studies using non-human animals have demonstrated that cocaine treatment can produce persistent deficits in executive functions, but there is relatively little evidence that treatment with cocaine produces persistent deficits in performance on hippocampal-dependent tasks. We recently demonstrated that extended (but not limited) access to self-administered cocaine is especially effective in producing persistent deficits on a test of cognitive vigilance, and therefore, we used this procedure to examine the effects of limited or extended access to cocaine self-administration on recognition memory performance, which is sensitive to hippocampal function. We found that extended access to cocaine produced deficits in recognition memory that persisted for at least 2 weeks after the cessation of drug use. We conclude that the deficits in learning and memory observed in cocaine addicts may be at least in part due to repeated drug use, rather than just due to a pre-existing condition, and that in studying the neural basis of such deficits procedures involving extended access to self-administered cocaine may be especially useful. Keywordsself-administration; memory; cocaine; object recognition Cocaine addicts present with a number of cognitive deficits even following prolonged abstinence. These include impaired performance on tasks involving attention and cognitive flexibility that are thought to be mediated by the medial and orbital prefrontal cortex, as well as spatial, verbal, and recognition memory impairments on tasks thought to be mediated by the hippocampus (Manschreck et al. 1990;Ardila et al. 1991;Berry et al. 1993;Beatty et al. 1995;Hoff et al. 1996;Bolla et al. 2003). Given that cognitive deficits are known to negatively impact treatment outcomes (Aharonovich et al. 2003;Aharonovich et al. 2006), the development of an animal model of persistent cocaine-induced cognitive deficits would be useful in exploring the nature of the deficit. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 July 31. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA number of preclinical studies have reported that treatment with cocaine produces cognit...

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Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Abstract: These findings suggest that adolescents are insensitive to cocaine-induced impairment of learning related to amygdala memory system functioning.

Cited by 39 publications

References 52 publications

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

Impaired object recognition following prolonged withdrawal from extended-access cocaine self-administration

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