Methylphenidate affects striatal dopamine differently in an animal model for attention-deficit/hyperactivity disorder--the spontaneously hypertensive rat.
The spontaneously hypertensive rat (SHR) is used as a model for attention-deficit/hyperactivity disorder (ADHD) because it has behavioural characteristics (hyperactivity, impulsiveness, poorly sustained attention) similar to those of ADHD. ADHD children have been shown to have reduced striatal activation in certain tasks. SHR have reduced striatal dopamine release in response to electrical stimulation. The present study set out to investigate possible long-term effects of methylphenidate treatment on dopaminergic function in striatal slices of SHR compared to their normotensive Wistar-Kyoto (WKY) control rats. Methylphenidate treatment (3 mg/kg daily for 14 days) did not normalize the decreased electrically-stimulated release of [(3)H]dopamine from SHR caudate-putamen slices nor did it affect postsynaptic D(2) receptor function. However, the second electrical stimulus caused a relatively greater release of [(3)H]dopamine from caudate-putamen slices of methylphenidate-treated SHR than from vehicle-treated SHR, suggesting that presynaptic mechanisms controlling dopamine release had been altered. Interestingly, [(3)H]dopamine release from WKY caudate-putamen slices in response to D(2) autoreceptor blockade by the antagonist, sulpiride, was selectively increased by methylphenidate treatment. This effect was not seen in SHR possibly because D(2) autoreceptor function had already been up-regulated. The results show that methylphenidate is unable to enhance D(2) autoreceptor function in SHR.
Russell
V A
VA
Department of Physiology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. russell@curie.uct.ac.za
de Villiers
A S
AS
Sagvolden
T
T
Lamm
M C
MC
Taljaard
J J
JJ
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000187:drug effects* / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D019257:Quinpirole; D013469:Sulpiride; D000109:Acetylcholine; D004298:Dopamine