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Effects of Topiramate on the Prepulse Inhibition of the Acoustic Startle in Rats
- Source :
- Neuropsychopharmacology. 32:320-331
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- The anticonvulsant topiramate (TPM) has been recently proposed as a novel adjuvant therapy for bipolar disorder and schizophrenia, yet its efficacy remains controversial. As both disorders are characterized by gating deficits, we tested the effects of TPM on the behavioral paradigm of prepulse inhibition (PPI) of the acoustic startle response, a validated animal model of sensorimotor gating. TPM (10, 18, 32, 58, 100 mg/kg, intraperitoneal, i.p.) enhanced PPI in rats in a dose-dependent fashion, prevented the PPI reduction mediated by the dopaminergic agonist apomorphine (0.25 mg/kg, subcutaneous, s.c.) and potentiated the effects of the antipsychotic drugs haloperidol (0.05, 0.1 mg/kg, i.p.) and clozapine (2.5, 5 mg/kg, i.p.). Conversely, TPM elicited no significant effect on the PPI disruption mediated by the NMDA receptor antagonist dizocilpine (0.05, 0.1 mg/kg, s.c.) and surprisingly antagonized the attenuation of dizocilpine-induced PPI disruption mediated by clozapine (5 mg/kg, i.p.). Our results suggest that TPM may exert diverse actions on the neural substrates of sensorimotor gating. While the pharmacological mechanisms of such effects are still elusive, our findings might contribute to shed light on some controversies on the therapeutic action of TPM, and point to this drug as a putative novel adjuvant therapy for some clusters of gating disturbances.
- Subjects :
- Male
Agonist
Reflex, Startle
medicine.medical_specialty
Startle response
Bipolar Disorder
medicine.drug_class
Dopamine
Glutamic Acid
Fructose
Gating
Pharmacology
Synaptic Transmission
Rats, Sprague-Dawley
Topiramate
Internal medicine
Haloperidol
Animals
Medicine
Prepulse inhibition
Clozapine
Dose-Response Relationship, Drug
medicine.diagnostic_test
business.industry
Brain
Drug Synergism
Neural Inhibition
Rats
Dizocilpine
Apomorphine
Psychiatry and Mental health
Endocrinology
Dopamine Agonists
Schizophrenia
Anticonvulsants
business
Excitatory Amino Acid Antagonists
Antipsychotic Agents
medicine.drug
Subjects
Details
- ISSN :
- 1740634X and 0893133X
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....81182299e7c18a4685b1861e9e0c471e