Preliminary evaluation of oral anticonvulsant treatment in the quinpirole model of bipolar disorder.

Abstract

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.

• Authors: A Shaldubina, H Einat, H Szechtman, H Shimon, R H Belmaker
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 109 Issue 3 Pg. 433-40 (Mar 2002) ISSN: 0300-9564 [Print] Austria
• PMID: 11956963 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticonvulsants
• Dopamine Agonists
• Receptors, Dopamine
• Topiramate
• Quinpirole
• Fructose
• Carbamazepine
• Valproic Acid
• Phenytoin

Topics

• Administration, Oral
• Animals
• Anticonvulsants (pharmacology)
• Bipolar Disorder (chemically induced, drug therapy, physiopathology)
• Brain (drug effects, metabolism, physiopathology)
• Carbamazepine (blood, pharmacology)
• Disease Models, Animal
• Dopamine Agonists (pharmacology)
• Drug Administration Schedule
• Fructose (analogs & derivatives, pharmacology)
• Hyperkinesis (chemically induced, drug therapy, physiopathology)
• Motor Activity (drug effects, physiology)
• Neurons (drug effects, metabolism)
• Phenytoin (blood, pharmacology)
• Quinpirole (pharmacology)
• Rats
• Receptors, Dopamine (drug effects, metabolism)
• Topiramate
• Valproic Acid (blood, pharmacology)