Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder.
A potential model for bipolar disorder, quinpirole-induced biphasic locomotion, was used for a preliminary evaluation of behavioral effects of oral anticonvulsant treatment. Quinpirole, a D2/D3 agonist, induces a biphasic locomotor response starting with inhibition and followed by excitation, resembling the oscillating nature of bipolar disorder. The present study developed a paradigm for oral administration of anticonvulsants that resulted in therapeutic blood levels and tested the effects of treatment on the quinpirole-induced response. Eleven days treatment with valproate (12 g/liter water), phenytoin (6 g/kg food), and carbamazepine (8 g/kg food) resulted in therapeutic blood levels and in a borderline significant reduction in quinpirole-induced hyperactivity without effects on the hypoactive phase. Valproate effects became more significant at the height of the hyperactivity response. Eleven days treatment with topiramate (30 mg/kg) resulted in a significant attenuation of quinpirole-induced hyperactivity, qualitatively similar to the effects of the other anticonvulsants. The results suggest that mood-stabilizing anticonvulsant drugs including topiramate may attenuate quinpirole-induced hyperactivity.
Shaldubina
A
A
Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Einat
H
H
Szechtman
H
H
Shimon
H
H
Belmaker
R H
RH
D000284:Administration, Oral; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002220:Carbamazepine / Q000097:blood / Q000494:pharmacology; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005632:Fructose / Q000031:analogs & derivatives / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010672:Phenytoin / Q000097:blood / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D000077236:Topiramate; D014635:Valproic Acid / Q000097:blood / Q000494:pharmacology
D000927:Anticonvulsants; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D000077236:Topiramate; D019257:Quinpirole; D005632:Fructose; D002220:Carbamazepine; D014635:Valproic Acid; D010672:Phenytoin