Methylphenidate does not increase ethanol consumption in a rat model for attention-deficit hyperactivity disorder-the spontaneously hypertensive rat.
Attention-deficit hyperactivity disorder (ADHD) is a behavioural disorder that has been suggested to result from disturbances in the dopaminergic system of the brain. The most effective drugs used to treat ADHD are the psychostimulants, methylphenidate and amphetamine. They block dopamine transporters and increase dopamine release, thereby increasing the extracellular concentration of dopamine and altering dopamine signaling. Drugs of abuse, such as cocaine, also block dopamine transporters, which raises the concern that treatment of children with ADHD with psychostimulants might increase their susceptibility to drug addiction. The present study was aimed at investigating whether treatment with methylphenidate at an early stage of development increased preference for ethanol in a widely used rat model for ADHD, the spontaneously hypertensive rat (SHR). SHR display the three major characteristics of ADHD (hyperactivity, impulsivity, poor sustained attention) compared to their progenitor Wistar-Kyoto (WKY) rat strain. Ethanol increased locomotor activity of SHR slightly more than WKY when injected intraperitoneally (0.6 g/kg). SHR also spent more time in the inner zone of the open field than WKY, consistent with SHR being less anxious than WKY. When given free access to ethanol-containing solutions of increasing concentration, SHR consumed less ethanol than WKY. Treatment with methylphenidate at an early age (P21 to P35) did not alter ethanol consumption in adult SHR or WKY, suggesting that it does not increase susceptibility to ethanol addiction in these rats. In vitro superfusion studies further demonstrated that preadolescent methylphenidate treatment did not have long-term effects on dopamine release in adult SHR and WKY striatum. A major finding of this study is the fact that methylphenidate treatment did not increase alcohol use in SHR.
Soeters
Heleen Suzanne
HS
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa.
Howells
Fleur Margaret
FM
Russell
Vivienne Ann
VA
D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000523:psychology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D011188:Potassium