Caffeine exposure sensitizes rats to the reinforcing effects of cocaine

Horger, Brian A.; Wellman, Paul J.; Morien, Annie; Davies, Becky T.; Schenk, Susan

doi:10.1097/00001756-199101000-00013

Cited by 99 publications

(68 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%

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

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

226

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%

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

Brandon

Marinelli²,

Baker

et al. 2001

Neuropsychopharmacology

226

147

View full text Add to dashboard Cite

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“…These findings are in opposition to other studies where acute treatment with caffeine in adult animals increases the development of cocaine CPP (Bedingfield et al, 1998), augments cocaine-induced locomotor activity (Horger et al, 1991;Misra et al, 1986), and results in amplified activation of the mesolimbic dopamine system (Horger et al, 1991). Likewise, chronic caffeine exposure in adult animals increased locomotor activity to cocaine (Gasior et al, 2000;Schenk et al, 1990) and facilitated acquisition of cocaine self-administration (Carroll and Lac, 1998).…”

Section: Discussioncontrasting

confidence: 58%

“…Caffeine increases the rewarding effects of cocaine through its ability to increase dopamine neurotransmission (Bedingfield et al, 1998;Horger et al, 1991;Misra et al, 1986;Solinas et al, 2002). We examined the effects of caffeine consumption during adolescence on cocainemediated behaviors and NAc neurobiology in adulthood following withdrawal from caffeine.…”

Section: Discussionmentioning

confidence: 99%

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

O’Neill

Levis

Schreiner

et al. 2014

Neuropsychopharmacol

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Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D 2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D 2 receptor, dopamine transporter, and adenosine A 1 receptor and decreased adenosine A 2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A 1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.

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“…Exposure to cocaine has been repeatedly demonstrated as a sufficient condition for the development of behavioral and neurochemical sensitization to subsequent administration of a variety of stimulants (Akimoto et al 1990;Elmer et al 1996). Although repeated administration of caffeine was ineffective in sensitizing rats to the behavioral effects of caffeine itself, preexposure rendered rats supersensitive to the behavioral effects of cocaine (Schenk et al 1989;Horger et al 1991). These findings suggest that repeated caffeine administration produced neuroadaptations in systems underlying the behavioral response to cocaine, and raise the possibility that the reverse condition is also true; that repeated exposure to cocaine via self-administration renders subjects more responsive to some of the effects of caffeine.…”

Section: Discussionmentioning

confidence: 99%