Preexposure sensitizes rats to the rewarding effects of cocaine

Horger, Brian A.; Shelton, Keith L.; Schenk, Susan

doi:10.1016/0091-3057(90)90552-s

Cited by 254 publications

(157 citation statements)

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“…Animal studies clearly show that pre-exposure to psychomotor stimulants enhances subsequent SA of such drugs (Horger et al 1990(Horger et al , 1991(Horger et al , 1992Pierre and Vezina 1997;Vezina et al 1999;Lorrain et al 2000). Consistent with pre-exposure to nicotine (Horger et al 1992), and low-dose exposure to amphetamine (Pierre and Vezina 1997) we found a differential effect of low-dose MP preexposure on the reinforcing and locomotor activating effects of cocaine.…”

Section: Adolescent Exposure To Mp Enhances Cocaine Self-administratisupporting

confidence: 82%

“…Unfortunately, animal studies have provided conflicting answers (Laviola et al 1995;Ujike et al 1995;Snyder et al 1998;Wood et al 1998;Izenwasser et al 1999;McDougall et al 1999;Zavala et al 2000). Sensitization to MP in rodent models has been well documented (Shuster et al 1982;Gaytan et al 1997;Crawford et al 1998; but see McNamara et al 1993), but the use of relatively high doses in most studies, and the apparent inability of MP to induce long-term locomotor sensitization in young animals (McDougall et al 1999), has raised questions regarding the clinical relevance of such findings (National Institute of Mental Health 1999).Animal studies have also shown that repeated exposure to psychostimulants increases the likelihood that rats will acquire drug self-administration (SA) with shorter latencies (Horger et al 1992) and at lower doses (Horger et al 1990), perhaps a more relevant display of sensitization as it relates to addiction. Pretreatment with such stimulants as nicotine, caffeine, and amphetamine produces enduring enhancements in the acquisition of cocaine SA (Valdez and Schenk 1994;Schenk and Davidson 1998).…”

mentioning

confidence: 99%

“…Animal studies have also shown that repeated exposure to psychostimulants increases the likelihood that rats will acquire drug self-administration (SA) with shorter latencies (Horger et al 1992) and at lower doses (Horger et al 1990), perhaps a more relevant display of sensitization as it relates to addiction. Pretreatment with such stimulants as nicotine, caffeine, and amphetamine produces enduring enhancements in the acquisition of cocaine SA (Valdez and Schenk 1994;Schenk and Davidson 1998).…”

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confidence: 99%

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Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

225

147

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Treatment of attention deficit hyperactivity disorder with the psychostimulant drug methylphenidate (MP) has increased dramatically among schoolchildren. We tested whether repeated exposure to moderate doses of MP (5 and 10 mg/kg IP for 5 or 7 days) in adolescent rats increased reactivity to cocaine measured by motor responses (ambulations and rearing) to a cocaine challenge in adulthood. We later tested whether repeated exposure to a low dose of MP (2 mg/kg IP for 7 days) enhanced the psychomotor effects of cocaine, measured by different challenge doses (0-30 mg/kg) as well as to the reinforcing effects of cocaine, measured by self-administration of lowdose infusion (75 g/kg, IV). We found that exposure to moderate doses of MP enhanced psychomotor responses to cocaine but exposure to a low dose only increased cocaine self-administration. These results suggest that adolescent exposure to low doses of MP in rats mayMethylphenidate (Ritalin ® ) is used widely in the treatment of attention deficit hyperactivity disorder (ADHD), the most commonly diagnosed disorder of childhood (Swanson et al. 1998). During the 1990s, diagnosis and treatment of this disorder grew dramatically in the United States. Estimates show that up to 15% of school age children may be affected in certain geographical locations (Scahill and Schwab-Stone 2000) and that prevalence is estimated to be 5-10% in the general population (Swanson et al. 1998). In addition, preschoolers (Zito et al. 2000) and children who do not meet the diagnostic criteria for ADHD (Marshall 2000) have recently been identified as two new groups increasingly exposed to this drug. The duration of treatment is several years in childhood, more often extending into adolescence and adulthood (Garland 1998;Robin 1999;Silver 2000;Spencer et al. 2000).Animal studies have shown that MP is a psychostimulant, which, as with cocaine, blocks the dopamine transporter (DAT) (Kuczenski and Segal 1997); thereby increasing extracellular dopamine (DA) levels in the striatum and nucleus accumbens (Kuczenski 1983), brain regions involved in the locomotor and reinforcing effects of psychostimulants and other drugs of abuse (Koob and Bloom 1988 NO . 5 et al. 1999). Oral therapeutic doses of MP effectively block more than 50% of DATs (Volkow et al. 1998); thereby increasing extracellular DA levels (Volkow et al. 2001). These actions are highly associated with the reinforcing properties of drugs (Ritz et al. 1987). Taken together, the well-documented abuse potential of psychostimulants (for reviews see White and Wolf 1991;Robinson and Berridge 1993;Self and Nestler 1995), studies linking ADHD with subsequent substance abuse (Wilens et al. 1997;Clure et al. 1999;Schubiner et al. 2000), and the dearth of controlled studies on the effects of long-term stimulant exposure on the brain, all make MP exposure an important public health issue.Animal models of drug addiction clearly indicate that repeated exposure to psychostimulants results in augmented behaviors (sensitization) that can be detected lo...

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Section: Adolescent Exposure To Mp Enhances Cocaine Self-administratisupporting

confidence: 82%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

225

147

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“…For example, self-administration of cocaine produces sensitization to the locomotor-activating effects (Hooks et al, 1994;Phillips and Di Ciano, 1996;Zapata et al, 2003;Ben-Shahar et al, 2004). It has also been demonstrated that rats receiving experimenter-administered stimulants, which produces a sensitized locomotor response, acquire selfadministration faster and/or at lower doses (Horger et al, 1990(Horger et al, , 1992Schenk et al, 1991). Animals treated this way also respond to higher breakpoints when subsequently tested on a PR schedule (Mendrek et al, 1998;Lorrain et al, 2000;Covington and Miczek, 2001;Suto et al, 2002Suto et al, , 2003Vezina et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Rapid and Persistent Sensitization to the Reinforcing Effects of Cocaine

Morgan

Liu

Roberts

2005

Neuropsychopharmacol

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The development of drug addiction involves a transition from recreational use to compulsive drug seeking and taking, and this progression can occur rapidly with cocaine use. These data highlight the importance of early drug exposure and the development of drug dependence; however, little experimental attention has been paid to this phenomenon in animal models of drug abuse. The present experiments demonstrate a progressive and rapid sensitization to the reinforcing strength of cocaine assessed using a progressive ratio (PR) schedule in rats. The first experiment found that rats show increased breakpoints over a 2-week period following acquisition. Subsequent experiments examined the role of total cocaine intake during the initial exposure period and found that low intakes (20 mg/ kg/day Â 5 days) resulted in sensitization, whereas relatively higher intake (60 or 100 mg/kg/day Â 5 days) suppressed the development of sensitization. In contrast, this higher level of intake (60 mg/kg/day Â 5 days) only transiently suppressed the expression of sensitization. Examination of breakpoints maintained by various doses of cocaine revealed an upward and leftward displacement of the cocaine doseeffect curve, relative to nonsensitized animals. These studies describe a form of sensitization that occurs rapidly to the reinforcing effects of cocaine, and provide a model to study the potential impact of initial experience on the development of drug dependence.

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“…A single exposure to cocaine can be sufficient to induce long-lasting sensitization to the locomotor stimulant effects of cocaine , possibly through long-term potentiation of dopamine neurons in the ventral tegmental area (VTA) (Ungless et al, 2001). Repeated intermittent pre-exposure to cocaine also facilitated the subsequent acquisition of cocaine self-administration (Horger et al, 1990;Piazza et al, 1990). Furthermore pre-exposure to, for example, amphetamine, cocaine, and morphine enhanced the conditioned motivational effects of the respective drug (Lett, 1989;Shippenberg and Heidbreder, 1995a).…”

Section: Introductionmentioning

confidence: 99%

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

Lesscher

Hordijk

Bondar

et al. 2004

Neuropsychopharmacol

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Although m-opioid receptors have been extensively investigated for their role in drug reinforcement, little is known about the contribution of these receptors to the acute and sensitized locomotor response to cocaine. In this study m-opioid receptor involvement in acute cocaine-induced locomotor activity and in the development of cocaine-induced behavioral sensitization was evaluated using mopioid receptor knockout mice and chronic naltrexone (NTX) pretreatment as models. In addition, co-administration of the specific mopioid receptor antagonist CTOP with repeated saline or cocaine injections was used to establish the involvement of m-opioid receptors in sensitization to the locomotor stimulant effects of cocaine. The acute locomotor response to cocaine (3, 10, 20, or 30 mg/kg i.p.) of mopioid receptor knockout or chronic NTX pretreated mice was not different from the cocaine response of their respective controls. With respect to cocaine-induced behavioral sensitization, induced by daily injections of 20 mg/kg cocaine for 11 subsequent days, mopioid receptor knockout mice developed behavioral sensitization to the locomotor stimulant effects of cocaine (challenge 10 mg/kg i.p.) comparable to wild-type littermates and the m-opioid receptor antagonist CTOP did not affect cocaine-induced sensitization either. However, mice that were pretreated with NTX exhibited augmented cocaine-induced behavioral sensitization relative to placebo pretreated controls, which may be ascribed to increased d-opioid receptor levels as has been described for chronic NTX pretreated mice. The present findings suggest that m-opioid receptors are not required for the acute locomotor response to cocaine nor are they essential for the development of cocaine-induced behavioral sensitization.

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Preexposure sensitizes rats to the rewarding effects of cocaine

Cited by 254 publications

References 14 publications

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Enhanced Reactivity and Vulnerability to Cocaine Following Methylphenidate Treatment in Adolescent Rats

Rapid and Persistent Sensitization to the Reinforcing Effects of Cocaine

μ-Opioid Receptors are not Involved in Acute Cocaine-Induced Locomotor Activity nor in Development of Cocaine-Induced Behavioral Sensitization in Mice

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