Psychopharmacology

, Volume 181, Issue 1, pp 38–47 | Cite as

Repeated administration of methylphenidate in young, adolescent, and mature rats affects the response to cocaine later in adulthood

Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

Previous studies have shown that the expression of behavioral sensitization to psychostimulants depends on the age and gender of the animal.

Objective

This study was conducted to determine the pattern of behavioral sensitization to repeated administration of methylphenidate (MPD) at three different developmental ages and to assess the response to a cocaine challenge in adulthood.

Methods

We gave five daily i.p. injections of 10 or 20 mg kg−1 of MPD (10 MPD, 20 MPD) or saline to male and female rats beginning on postnatal days (PND) 21, 45, or 60. When all groups reached PND 90, rats were challenged with 10 mg kg−1 cocaine. For both MPD administration and cocaine challenge, locomotion and stereotyped behaviors were assessed for 1 h.

Results

The 10 MPD dose produced increased locomotion over the other two treatments at all ages. Rats that received 20 MPD showed a decline in locomotion across days with an increase in the time spent in high intensity stereotypy by day 5. Animals treated with 10 MPD showed diverse behavioral responses with adolescents showing somewhat dampened stereotypy than the other two age groups. In response to cocaine, pretreatment with MPD at all ages enhanced the cocaine response and produced qualitatively different patterns of stereotyped behavior for each gender and pretreatment age group.

Conclusion

MPD produced clear age-specific sensitization of behavior in rats. Furthermore, exposure to MPD cross-sensitized with cocaine regardless of the age at which MPD exposure occurred with each pretreatment age group showing a unique pattern of responses.

Keywords

Methylphenidate Adolescence Gender differences Cocaine Locomotion Stereotypy 

Abbreviations

MPD

methylphenidate

PND

postnatal days

i.p.

intraperitoneal

This is a preview of subscription content, log in to check access.

Notes

Acknowledgements

The authors would like to acknowledge the technical assistance of Lucille Grullon and Stacy Stephenson. Susan Melnick, Ph.D., contributed to the data collection. Statistical advice from Jeremy Weedon, Ph.D., is also appreciated. This work was supported by NIH NIDA RO1DA 10990 to D.D.E. and The American Psychological Association, Diversity in Neuroscience Fellowship to A.T.R.

References

  1. Andersen SL, Arvanitogiannis A, Pliakas AM, LeBlanc C, Carlezon WA Jr (2002) Altered responsiveness to cocaine in rats exposed to methylphenidate during development. Nat Neurosci 5:13–14CrossRefPubMedGoogle Scholar
  2. Becker JB (1999) Gender differences in dopaminergic function in striatum and nucleus accumbens. Pharmacol Biochem Behav 64:803–812CrossRefPubMedGoogle Scholar
  3. Bowman BP, Vaughan SR, Walker QD, Davis SL, Little PJ, Scheffler NM, Thomas BF, Kuhn CM (1999) Effects of sex and gonadectomy on cocaine metabolism in the rat. J Pharmacol Exp Ther 290(3):1316–1323PubMedGoogle Scholar
  4. Brandon CL, Marinelli M, Baker LK, White FJ (2001) Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats. Neuropsychopharmacology 25:651–661CrossRefPubMedGoogle Scholar
  5. Crawford CA, McDougall SA, Meier TL, Collins RL, Watson JB (1998) Repeated methylphenidate treatment induces behavioral sensitization and decreases protein kinase A and dopamine-stimulated adenyl cyclase activity in the dorsal striatum. Psychopharmacology 136:34–43CrossRefPubMedGoogle Scholar
  6. Di Paolo T (1994) Modulation of brain dopamine transmission by sex steroids. Rev Neurosci 5:27–41PubMedGoogle Scholar
  7. Fog R (1969) Stereotyped and non-stereotyped behaviour in rats induced by various stimulant drugs. Psychopharmacologia 14:299–304PubMedCrossRefGoogle Scholar
  8. Gatley SJ, Volkow ND, Gifford AN, Fowler JS, Dewey SL, Ding Y-S, Logan J (1999) Dopamine-transporter occupancy after intravenous doses of cocaine and methylphenidate in mice and humans. Psychopharmacology 146:93–100CrossRefPubMedGoogle Scholar
  9. Gaytan O, al-Rahim S, Swann A, Dafny N (1997) Sensitization to locomotor effects of methylphenidate in the rat. Life Sci 61:PL101–PL107CrossRefPubMedGoogle Scholar
  10. Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D (1999) Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol 373:187–193CrossRefPubMedGoogle Scholar
  11. Kolta MG, Scalzo FM, Ali SF, Holson RR (1990) Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats. Psychopharmacology 100:377–382PubMedCrossRefGoogle Scholar
  12. Laviola G, Wood RD, Kuhn C, Francis R, Spear L (1995) Cocaine sensitization in periadolescent and adult rats. J Pharmacol Exp Ther 275:345–357PubMedGoogle Scholar
  13. Levine B, Caplan YH, Kauffman G (1986) Fatality resulting from methylphenidate overdose. J Anal Toxicol 10:209–210PubMedGoogle Scholar
  14. McDougall SA, Collins RL, Karper PE, Watson JB, Crawford CA (1999) Effects of repeated methylphenidate treatment in the young rat: sensitization of both locomotor activity and stereotyped sniffing. Exp Clin Psychopharmacol 7:208–218CrossRefPubMedGoogle Scholar
  15. McNamara CG, Davidson ES, Schenk S (1993) A comparison of the motor-activating effects of acute and chronic exposure to amphetamine and methylphenidate. Pharmacol Biochem Behav 45:729–732CrossRefPubMedGoogle Scholar
  16. Melnick SM, Dow-Edwards DL (2001) Differential behavioral responses to chronic amphetamine in adult male and female rats exposed to postnatal cocaine treatment. Pharmacol Biochem Behav 69:219–224CrossRefPubMedGoogle Scholar
  17. Meririnne E, Kankaanpaa A, Seppala T (2001) Rewarding properties of methylphenidate: sensitization by prior exposure to the drug and effects of dopamine D1- and D2-receptor antagonists. J Pharmacol Exp Ther 298:539–550PubMedGoogle Scholar
  18. Morton WA, Stockton GG (2000) Methylphenidate abuse and psychiatric side effects. Prim Care Companion J Clin Psychiat 2:159–164Google Scholar
  19. Pierce RC, Kalivas PW (1997) A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev 25:192–216PubMedCrossRefGoogle Scholar
  20. Schenk S, Izenwasser S (2002) Pretreatment with methylphenidate sensitizes rats to the reinforcing effects of cocaine. Pharmacol Biochem Behav 72:651–657CrossRefPubMedGoogle Scholar
  21. Spear L (2000) The adolescent brain and age-related behavioral manifestations. Neurosci Biobehav Rev 24:417–463CrossRefPubMedGoogle Scholar
  22. Torres-Reveron A, Melnick SM, Dow-Edwards DL (2003) Ontogeny of Methylphenidate sensitization. Abstract Viewer/Itinerary Planner Program No. 324.13Google Scholar
  23. Ujike H, Tsuchida K, Akiyama K, Fujiwara Y, Kuroda S (1995) Ontogeny of behavioral sensitization to cocaine. Pharmacol Biochem Behav 50:613–617CrossRefPubMedGoogle Scholar
  24. Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ (2002) Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord 6(Suppl 1):S31–S43PubMedGoogle Scholar
  25. Wood RD, Tirelli E, Snyder KJ, Heyser CJ, LaRocca TM, Spear LP (1998) Evidence for behavioral sensitization to cocaine in preweanling rat pups. Psychopharmacology (Berl) 138:114–123CrossRefGoogle Scholar
  26. Yang PB, Swann AC, Dafny N (2003) Chronic pretreatment with methylphenidate induces cross-sensitization with amphetamine. Life Sci 73:2899–2911CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Annelyn Torres-Reverón
    • 1
  • Diana L. Dow-Edwards
    • 1
    • 2
  1. 1.Program in Neural and Behavioral Sciences and Department of Physiology and PharmacologyState University of New York Health Sciences Center at BrooklynBrooklynUSA
  2. 2.BrooklynUSA

Personalised recommendations