Psychopharmacology

, Volume 204, Issue 3, pp 551–562 | Cite as

Nicotinic receptors differentially modulate the induction and expression of behavioral sensitization to methylphenidate in rats

Original Investigation

Abstract

Rationale

Nicotinic acetylcholine receptors (nAChRs) regulate sensitization to stimulant drugs such as d-amphetamine and cocaine.

Objectives

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-β-erythroidine (DHβE; 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 DHβE. 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 β2 subunit nAChRs attenuates the induction of behavioral sensitization to high doses of methylphenidate.

Keywords

Methylphenidate Mecamylamine DHβE Rat Locomotor activity Sensitization Antagonist Nicotinic receptor 

Abbreviations

nAChR

Nicotinic acetylcholine receptor

ADHD

Attention-deficit/hyperactivity disorder

DHβE

Dihydro-β-erythoroidine

ACh

Acetylcholine

DA

Dopamine

5-HT

Serotonin

NAcc

Nucleus accumbens

VTA

Ventral tegmental area

Notes

Acknowledgements

We gratefully acknowledge the technical assistance of Blake Dennis and Joshua Cutshall. This work was supported by USPHS grants DA 023853 and DA 017548.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of Psychology, College of Arts and SciencesUniversity of KentuckyLexingtonUSA
  2. 2.Department of Psychology, BBSRB, Room 447University of KentuckyLexingtonUSA

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