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An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition.
J Pharmacol Exp Ther. 2005 Dec; 315(3):1163-71.JP

Abstract

Acutely manic bipolar patients, like patients with schizophrenia, Tourette's syndrome, panic disorder, and obsessive compulsive disorder, exhibit deficits in sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle response. Here, we assessed the ability of four drugs used in the treatment of bipolar mania-phenytoin, carbamazepine, valproate, and lithium-to reduce the PPI-disruptive effects of ketamine or amphetamine in the 129SvPasIco inbred strain of mice. For comparison, we also assessed the interaction of lithium and amphetamine in C57BL/6J mice. This set of studies yielded four major results. 1) Lithium chloride (85 mg/kg) prevented amphetamine-induced but not ketamine-induced disruption of PPI in both strains of mice. 2) Carbamazepine (50 mg/kg) prevented ketamine-induced but not amphetamine-induced disruption of PPI. 3) Sodium valproate (100 mg/kg) did not prevent amphetamine- or ketamine-induced disruption of PPI. 4) Phenytoin (30 mg/kg) did not prevent amphetamine- or ketamine-induced disruption of PPI but increased PPI on its own. These studies did not reveal a consistent relationship between the ability of a drug to protect PPI from disruption by ketamine or amphetamine and efficacy in the treatment of bipolar mania. Instead, the diverse effect profiles of these four treatments in reversing the PPI deficits produced by amphetamine or ketamine in mice presumably reflect the differences in their respective pharmacological mechanisms. Hence, further studies using these dopaminergic and glutamatergic models of deficient PPI may provide valuable insights into the mechanisms underlying the differential therapeutic effects of antimanic and mood-stabilizing treatments.

Authors+Show Affiliations

Ong JC
Department of Psychiatry, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA.
Brody SA
No affiliation info available
Large CH
No affiliation info available
Geyer MA
No affiliation info available

MeSH

AmphetamineAnesthetics, DissociativeAnimalsAntimanic AgentsCarbamazepineCentral Nervous System StimulantsDose-Response Relationship, DrugDrug InteractionsKetamineLithiumMaleMiceMice, Inbred C57BLMice, Inbred StrainsPhenytoinReflex, StartleValproic Acid

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16123308

Citation

Ong, Jacob C., et al. "An Investigation of the Efficacy of Mood Stabilizers in Rodent Models of Prepulse Inhibition." The Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 3, 2005, pp. 1163-71.
Ong JC, Brody SA, Large CH, et al. An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition. J Pharmacol Exp Ther. 2005;315(3):1163-71.
Ong, J. C., Brody, S. A., Large, C. H., & Geyer, M. A. (2005). An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition. The Journal of Pharmacology and Experimental Therapeutics, 315(3), 1163-71.
Ong JC, et al. An Investigation of the Efficacy of Mood Stabilizers in Rodent Models of Prepulse Inhibition. J Pharmacol Exp Ther. 2005;315(3):1163-71. PubMed PMID: 16123308.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - An investigation of the efficacy of mood stabilizers in rodent models of prepulse inhibition. AU - Ong,Jacob C, AU - Brody,Suzanne A, AU - Large,Charles H, AU - Geyer,Mark A, Y1 - 2005/08/25/ PY - 2005/8/27/pubmed PY - 2006/1/24/medline PY - 2005/8/27/entrez SP - 1163 EP - 71 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 315 IS - 3 N2 - Acutely manic bipolar patients, like patients with schizophrenia, Tourette's syndrome, panic disorder, and obsessive compulsive disorder, exhibit deficits in sensorimotor gating, as measured by prepulse inhibition (PPI) of the startle response. Here, we assessed the ability of four drugs used in the treatment of bipolar mania-phenytoin, carbamazepine, valproate, and lithium-to reduce the PPI-disruptive effects of ketamine or amphetamine in the 129SvPasIco inbred strain of mice. For comparison, we also assessed the interaction of lithium and amphetamine in C57BL/6J mice. This set of studies yielded four major results. 1) Lithium chloride (85 mg/kg) prevented amphetamine-induced but not ketamine-induced disruption of PPI in both strains of mice. 2) Carbamazepine (50 mg/kg) prevented ketamine-induced but not amphetamine-induced disruption of PPI. 3) Sodium valproate (100 mg/kg) did not prevent amphetamine- or ketamine-induced disruption of PPI. 4) Phenytoin (30 mg/kg) did not prevent amphetamine- or ketamine-induced disruption of PPI but increased PPI on its own. These studies did not reveal a consistent relationship between the ability of a drug to protect PPI from disruption by ketamine or amphetamine and efficacy in the treatment of bipolar mania. Instead, the diverse effect profiles of these four treatments in reversing the PPI deficits produced by amphetamine or ketamine in mice presumably reflect the differences in their respective pharmacological mechanisms. Hence, further studies using these dopaminergic and glutamatergic models of deficient PPI may provide valuable insights into the mechanisms underlying the differential therapeutic effects of antimanic and mood-stabilizing treatments. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/16123308/An_investigation_of_the_efficacy_of_mood_stabilizers_in_rodent_models_of_prepulse_inhibition_ DB - PRIME DP - Unbound Medicine ER -