Nicotinic receptors differentially modulate the induction and expression of behavioral sensitization to methylphenidate in rats.
BACKGROUND
Nicotinic acetylcholine receptors (nAChRs) regulate sensitization to stimulant drugs such as d-amphetamine and cocaine.


OBJECTIVE
The current study determined if nAChRs modulate the induction and/or expression of behavioral sensitization to high methylphenidate doses.


METHODS
In experiment 1, rats received saline or mecamylamine (3 mg/kg, sc), followed by saline or methylphenidate (5.6 or 10 mg/kg, sc) during 10 daily sessions; the effect of methylphenidate (1-17 mg/kg, sc) alone was determined 14 days later. In experiment 2, rats received saline or dihydro-beta-erythroidine (DHbetaE; 3 mg/kg, sc), followed by saline or 5.6 mg/kg of methylphenidate. In experiment 3, rats received saline or methylphenidate (5.6 or 10 mg/kg, sc) alone for 10 days; the effect of acute mecamylamine (3 mg/kg, sc) on the response to methylphenidate (1-17 mg/kg, sc) was determined 14 days later. Locomotor activity, sniffing, rearing, grooming, and stereotypy ratings were dependent measures.


RESULTS
Methylphenidate produced dose-dependent increases in locomotor activity, sniffing, and stereotypy on day 1 and these effects were enhanced on day 10, indicative of sensitization. Mecamylamine attenuated methylphenidate-induced stereotypy only on day 1, but reduced locomotor activity, sniffing, rearing, and stereotypy on day 10 and during the methylphenidate challenge phase; similar results were obtained with DHbetaE. However, acute mecamylamine did not alter the effects of the methylphenidate challenge following the induction of sensitization to methylphenidate alone.


CONCLUSIONS
Although nAChRs do not appear to regulate the expression of methylphenidate-induced behavioral sensitization, inhibition of high-affinity beta2 subunit nAChRs attenuates the induction of behavioral sensitization to high doses of methylphenidate.
Wooters
Thomas E
TE
Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, KY 40536-0509, USA.
Bardo
Michael T
MT
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D019966:Substance-Related Disorders / Q000523:psychology
D000697:Central Nervous System Stimulants; D011978:Receptors, Nicotinic; D008774:Methylphenidate; D004079:Dihydro-beta-Erythroidine