Rewarding properties of methylphenidate: sensitization by prior exposure to the drug and effects of dopamine D1- and D2-receptor antagonists.
In drug addiction, a sensitization phenomenon has been postulated to play a critical role. The aim of our study was to evaluate whether sensitization occurs to the rewarding properties of methylphenidate, a psychostimulant drug known to possess abuse potential, as assessed with the biased conditioned place preference method in rats. In addition, since the brain dopaminergic system is considered to be important in drug-reward, the involvement of dopamine D1- and D2-receptors both in the rewarding properties of methylphenidate and in sensitization to these properties was assessed. Conditioning with methylphenidate at doses of 1.25 to 20 mg/kg increased preference for the paired environment, whereas a dose of 0.31 mg/kg was ineffective. However, following the 7-day sensitization treatment with methylphenidate (0.62-20 mg/kg), conditioning with a dose of 0.31 mg/kg resulted in an increased preference for the paired environment, i.e., the rewarding properties of methylphenidate appeared to be sensitized. Control experiments indicated that the enhancement of preference was not due to attenuation of sensitization treatment-induced withdrawal nor to tolerance to aversive properties of methylphenidate. When conditioned with methylphenidate, D1-antagonist SCH 23390 but not D2-antagonist raclopride prevented place preference. However, when coadministered with methylphenidate during the sensitization treatment, both SCH 23390 and raclopride prevented the development of sensitization. These data indicate that the rewarding properties of methylphenidate are sensitized by prior exposure to the drug and that both D1- and D2-receptors, the latter of which possibly more specifically, appear to be involved in the development of this sensitization.
Meririnne
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National Public Health Institute, Department of Mental Health and Alcohol Research, Drug Research Unit, Helsinki, Finland. esa.meririnne@ktl.fi
Kankaanpää
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Seppälä
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D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D001552:Benzazepines / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004435:Eating / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013649:Taste / Q000187:drug effects
D001552:Benzazepines; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D008774:Methylphenidate; D020891:Raclopride