Different adaptations in ventral tegmental area dopamine neurons in control and ethanol exposed rats after methylphenidate treatment.
BACKGROUND
Methylphenidate (MPH) is a psychostimulant effective in treating attention-deficit/hyperactivity disorder (ADHD). Repeated MPH treatment may increase substance abuse risk because of adaptations in dopaminergic (DA) function associated with sensitization to subsequent stimulant exposure. However, this possibility is based on observations in normal animals and may not apply to animals with attention problems linked to compromised DA function such as prenatal ethanol exposed (PE) animals.


METHODS
The electrical activity of ventral tegmental area (VTA) DA neurons was studied after the cessation of repeated MPH treatment at a threshold dose (1 mg/kg/day for 3 weeks) in PE and control rats.


RESULTS
In control rats, there was a continuous increase in VTA DA neuron excitability post-MPH treatment, characterized by a transient increase in population activity (1 day posttreatment) followed by decreased population activity (30-60 days posttreatment) in most of the animals due to depolarization inactivation. In PE rats, MPH treatment decreased the excessive excitability of VTA DA neurons and resulted in prolonged normalization in the population activity (1-60 days posttreatment). These changes were not mediated by altered sensitivity of somatodendritic DA autoreceptors.


CONCLUSIONS
Repeated MPH treatment produced distinctly different effects on VTA DA neuron activity in control and PE animals. These results suggest that repeated MPH treatment for ADHD may not lead to increased substance abuse risk in special populations such as individuals with fetal alcohol spectrum disorder.
Shen
Roh-Yu
RY
Research Institute on Addictions, State University of New York at Buffalo, Buffalo, New York 14203, USA. shen@ria.buffalo.edu
Choong
Kar-Chan
KC
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004567:Electrodes, Implanted; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017557:Ventral Tegmental Area / Q000187:drug effects*
D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D008774:Methylphenidate; D000431:Ethanol; D001058:Apomorphine; D004298:Dopamine