Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats

Behavioral and Brain Functions

Leora Yetnikoff¹  Andreas Arvanitogiannis² 

[1] Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, St Louis, MO, USA

[2] Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada

关键词: Wistar Kyoto;    Spontaneously hypertensive rat;    Sprague dawley;    Stimulant drugs;    Sensitization;    Strain differences;   

Others  :  793195
DOI  :  10.1186/1744-9081-9-38

 received in 2013-07-05, accepted in 2013-10-11,  发布年份 2013

【 摘 要 】

Background

Behavioral effects of stimulant drugs are influenced by non-pharmacological factors, including genetic variability and age. We examined acute and sensitized locomotor effects of methylphenidate in adolescent and early adult male Sprague Dawley (SD), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats using a drug regimen that differentiates clearly between initial and enduring differences in drug responsiveness. We probed for strain and age differences in the sensitizing effects of methylphenidate using a cocaine challenge. Methylphenidate was administered to the rats in a non-home environment.

Findings

Strain differences in sensitivity to single methylphenidate injections depend on age and change with continuing drug pretreatment. While SHR rats are more sensitive to methylphenidate relative to WKY regardless of age and pretreatment day, SHR rats become more sensitive to methylphenidate than SD rats towards the end of pretreatment during early adulthood. SD rats exhibit greater sensitivity to methylphenidate relative to the WKY group during adolescence, an effect that dissipates with continued drug pretreatment during adulthood. Remarkably, only SHR rats, regardless of age, exhibit methylphenidate-induced cross-sensitization to the behavioral effects of cocaine.

Conclusions

Our findings suggest that SHR rats are more vulnerable than other strains to methylphenidate-induced cross-sensitization to cocaine, at least when methylphenidate is administered in a non-home environment. Given that SHR rats are typically used to model features of attention deficit hyperactivity disorder, these findings may have important implications for the treatment of this disorder with methylphenidate.

【 授权许可】

   
2013 Yetnikoff and Arvanitogiannis; licensee BioMed Central Ltd.

【 图 表 】

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