Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents

Despite fears that using psychostimulants to treat patients with ADHD and co-occurring SUDs  (especially those with a history of stimulant use disorders) would exacerbate their SUDs, the evidence suggests that they are safe and effective in reducing core ADHD symptoms as well as possibly decreasing substance abuse (1,2). Furthermore, they may serve as a protective factor to decrease the longitudinal risk of developing a SUD in patients with ADHD as the index disorder (3).

1. Wilson JJ, Levin FR. Attention-Deficit/Hyperactivity Disorder and Early-Onset Substance Use Disorders. Journal of Child and Adolescent Psychopharmacology. 2005;15(5):751-763.
2. Levin FR, Evans SM, McDowell D, Kleber HD. Methylphenidate treatment for cocaine abusers with adult attention-deficit/hyperactivity disorder: A pilot study. J Clin Psychiatry. 1998;59:300-305.
3. Wilens TE, Faraone S, Biederman J, et al. Does stimulant therapy of ADHD beget later substance abuse: a meta-analytic review of the literature. Pediatrics. 2003;11(1):179-185.

Steve

Stephen Ross MD
Assistant Professor of Psychiatry
Director, Division of Alcoholism and Drug Abuse, Bellevue Hospital
Associate Director for Education
NYU School of Medicine
(212) 562-4097; fax (212) 562-2041

methylphenidate risk for cocaine response?

So.... if your kid is going to go on ADHD drugs.... better make sure it's for a long time or else you might increase the risk of the kid becoming a cocaine abuser?
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0N-4NWWW5W-1&_user=861681&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000046147&_version=1&_urlVersion=0&_userid=861681&md5=099ab83c01636eac1d7b31f8e6e09e6c

Effects of chronic oral methylphenidate on cocaine self-administration and striatal dopamine D2 receptors in rodents

Panayotis K. Thanos, Michael Michaelides, Helene Benveniste, Gene Jack Wang and Nora D. Volkow

Abstract

Background

Methylphenidate (MP) and amphetamine, which are the mainstay for the treatment of ADHD, have raised concerns because of their reinforcing effects and the fear that their chronic use during childhood or adolescence could induce changes in the brain that could facilitate drug abuse in adulthood.

Methods

Here we measured the effects of chronic treatment (8 months) with oral MP (1 or 2 mg/kg), which was initiated in periadolescent rats (postnatal day 30). Following this treatment, rats were tested on cocaine self-administration. In addition at 2 and 8 months of treatment we measured dopamine D2 receptor (D2R) availability in the striatum using [11C]raclopride microPET (μPET) imaging.

Results

Animals treated for 8 months with 2 mg/kg of MP showed significantly reduced rates of cocaine self-administration at adulthood than vehicle treated rats. D2R availability in the striatum was significantly lower in rats after 2 months of treatment with MP (1 and 2 mg/kg) but significantly higher after 8 months of MP treatment than in the vehicle treated rats. In vehicle treated rats D2R availability decreased with age whereas it increased in rats treated with MP. Because low D2R levels in the striatum are associated with a propensity for self-administration of drugs both in laboratory animals and in humans, this effect could underlie the lower rates of cocaine self-administration observed in the rats given 8 months of treatment with MP.

Conclusions

Eight month treatment with oral MP beginning in adolescence decreased cocaine-self administration (1 mg/kg) during adulthood which could reflect the increases in D2R availability observed at this life stage since D2R increases are associated with reduced propensity for cocaine self administration.

In contrast, two month treatment with MP started also at adolescence decreased D2R availability, which could raise concern that at this life stage short treatments could possibly increase vulnerability to drug abuse during adulthood.

These findings indicate that MP effects on D2R expression in the striatum are sensitive not only to length of treatment but also to the developmental stage at which treatment is given.

Future studies evaluating the effects of different lengths of treatment on drug self-administration are required to assess optimal duration of treatment regimes to minimize adverse effects on the propensity for drug self administration.