Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats

Mantsch, John R.; Yuferov, Vadim; Mathieu-Kia, Anne-Marie; Ho, Ann; Kreek, Mary Jeanne

doi:10.1007/s00213-004-1778-x

Cited by 195 publications

(213 citation statements)

References 45 publications

(52 reference statements)

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“…Most studies that have examined differential access regimens have focused on cocaine i.v. intake, with reports of escalated increases (Ahmed and Koob 1998;Mantsch et al 2004;Morgan et al 2002) or no changes (Dalley et al 2005;Kippin et al 2006;Roth and Carroll 2004b) over time. In addition to cumulative changes in drug intake, it has been argued that increased intake seen during the first hour of daily long-access self-administration of cocaine or heroin reflects allostatic decreases in reward function (Ahmed and Koob 2005).…”

Section: Discussionmentioning

confidence: 99%

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

2008

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Rationale-Methamphetamine is a highly addictive psychostimulant, and chronic methamphetamine users show high rates of relapse. Furthermore, prolonged methamphetamine abuse can lead to psychiatric symptoms and has been associated with various cognitive dysfunctions. However, the impact of self-administered methamphetamine on cognitive dysfunction and relapse has not been concurrently examined in an animal model.Objectives-The present study determined the effects of short-vs. long-access contingent methamphetamine on self-administration, extinction responding, reinstatement of methamphetamine seeking, and cognitive performance on an object exploration task.Materials and methods-Long-Evans rats self-administered methamphetamine i.v. (0.02 mg/ infusion) or received saline during daily sessions (1 or 2 h) for 10 days, followed by either maintained short-(1 or 2 h) or long-access (6 h) self-administration for 14 days. Lever responding was extinguished prior to reinstatement, which consisted of presentation of drug-paired cues or a priming injection of methamphetamine (1.0 mg/kg). Animals were also tested on an object exploration task prior to self-administration and at 10−12 days after cessation of self-administration, thus providing a comparison of pre-methamphetamine exposure with post-methamphetamine exposure.Results-Long-access methamphetamine self-administration resulted in escalation of daily intake. Furthermore, animals in both short-and long-access groups showed robust conditioned-cued and drug-primed reinstatement, with long access resulting in enhanced methamphetamine-primed reinstatement. Methamphetamine self-administration also led to access-dependent impairments on novel object recognition but failed to impair recognition of spatial reconfiguration.Conclusions-Extended methamphetamine self-administration enhances drug-primed reinstatement and decreases novel object recognition, indicating that prolonged contingent methamphetamine increases motivation for drug seeking following withdrawal while increasing cognitive deficits.

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Section: Discussionmentioning

confidence: 99%

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

2008

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“…This procedure was used to speed up escalation of heroin intake by LgA rats (Mantsch et al, 2004;. However, it has the disadvantage of confounding dose with time of access.…”

Section: Discussionmentioning

confidence: 99%

“…During the escalation phase, one group had access to heroin self-administration for only 1 h per day (ShA rats, n ¼ 12) and the other group for 6 h per day (LgA rats, n ¼ 12). To speed up the escalation process, the unit dose of heroin available during the past 5 h of each longaccess session was increased to 60 mg (by increasing the injection volume to 296 ml) (Mantsch et al, 2004;Wee et al, 2007). Self-administration sessions were run 6 days per week.…”

Section: Differential Access To IV Heroin Self-administrationmentioning

confidence: 99%

“…In contrast, with 6 or more hours of access per day (long access or LgA), rate of drug intake gradually escalates above initial levels (Ahmed and Koob, 1998;Ahmed et al, 2000;Mantsch et al, 2001;Paterson and Markou, 2003;Walker et al, 2003;Ferrario et al, 2005;Liu et al, 2005;Perry et al, 2006). The intensity of drug intake escalation is influenced by both the unit dose and the daily duration of drug access (Mantsch et al, 2004;Wee et al, 2007). Finally, once established, escalated levels of drug consumption can persist for several weeks, despite temporally reduced drug availability (Ahmed and Koob, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Lenoir

Ahmed

2007

Neuropsychopharmacol

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Escalation of drug consumptionFa hallmark of addictionFhas been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

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“…The regulation of mesolimbic Homer protein expression by cocaine has also been assessed in a "long access" animal model of addiction in which groups of animals are allowed to self-administer intravenous cocaine daily for either 1 hr or 6 hrs [e.g., [230][231][232]. These two self-administration paradigms elicit very different patterns of cocaine intake (stable vs. escalating, respectively) [e.g., 230] and result in very different neuroadaptations, as revealed by both behavioral and biochemical assays [230][231][232][233][234][235][236][237]. The effects of a history of cocaine self-administration upon corticoaccumbens CC-Homer expression are complex, dependent upon the duration of cocaine access, the duration of withdrawal and the region investigated (Table 2) [167,237].…”

Section: Homers and Cocaine-induced Neuroplasticitymentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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Effects of extended access to high versus low cocaine doses on self-administration, cocaine-induced reinstatement and brain mRNA levels in rats

Cited by 195 publications

References 45 publications

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Homers regulate drug-induced neuroplasticity: Implications for addiction

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