Article thumbnail
Location of Repository

Comparison of the Efficacy of two Anticonvulsants, Phenytoin and Valproate to Improve PCP and d-amphetamine Induced Deficits in a Reversal Learning Task in the Rat

By Nagi F. Idris, Jo C. Neill and Charles H. Large

Abstract

Recent studies in our laboratory have shown that PCP (phencyclidine) and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5 mg/kg and d-amphetamine at 0.5 mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25–200 mg/kg) and phenytoin (25–50 mg/kg) had no effect on performance when administered alone. Valproate (100–200 mg/kg), whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50 mg/kg), a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders

Topics: Neuroscience
Publisher: Frontiers Research Foundation
OAI identifier: oai:pubmedcentral.nih.gov:2701680
Provided by: PubMed Central

Suggested articles

Citations

  1. (1999). A glutamatergic defi ciency model of schizophrenia.
  2. (1997). A pivotal role for glutamate in the pathogenesis of schizophrenia, and its cognitive dysfunction.
  3. (1997). A two-process theory of schizophrenia: evidence from studies in post-mortem brain.
  4. (1997). Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex.
  5. (2002). Acute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain.
  6. (2005). An investigation of the effi cacy of mood stabilizers in rodent models of prepulse inhibition.
  7. (2002). Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity.
  8. (2002). Antiepileptic drugs in psychiatry: focus on randomized controlled trial.
  9. (2006). Clozapine application in prefrontal cortex blocks the effects of systemic MK-801 on extracellular 5-HT and glutamate.
  10. (1999). Clozapine plus lamotrigine in treatment resistant schizophrenia.
  11. (1998). Comparison of glutamate and gamma-aminobutyric acid uptake binding sites in frontal and temporal lobes in schizophrenia.
  12. (2009). Comparison of the effi cacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced defi cits in a reversal learning task in the rat.
  13. (1998). Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine.
  14. (2007). Do NMDA receptor antagonist models of schizophrenia predict the clinical effi cacy of antipsychotic drugs?
  15. (2000). Early identifi cation of refractory epilepsy.
  16. (1996). Effect of carbamazepine, oxcarbazepine and lamotrigine on the increase in extracellular glutamate elicited by veratridine in rat cortex and striatum.
  17. (1978). Effect of N- dipropylacetate on amino acid concentrations in mouse brain: correlations with anti- convulsant.
  18. (1999). Effects of anticonvulsants on veratridine- and KCl-evoked glutamate release from rat cortical synaptosomes.
  19. (2005). Evaluation of the effects of lamotrigine, valproate and carbamazepine in a rodent model of mania.
  20. (1997). Familial and developmental abnormalities of frontal lobe function and neurochemistry in schizophrenia.
  21. (1989). Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia.
  22. (2000). Functional brain imaging of schizophrenia. In The Psychopharmacology of Idris et al. Phenytoin and valproate Frontiers in Behavioral Neuroscience www.frontiersin.org
  23. (1995). Glutamate receptor dysfunction and schizophrenia.
  24. (1999). Glutamatergic aspects of schizophrenia.
  25. (2003). Induction of metabolic hypofunction and neurochemical deficits after chronic intermittent exposure to phencyclidine: differential modulation by antipsychotic drugs.
  26. (2005). Investigation of the effect of lamotrigine and clozapine to improve reversal learning impairments induced by acute PCP and d-amphetamine in the rat.
  27. (1997). Mechanisms of action of new antiepileptic drugs.
  28. (1987). Negative schizophrenia symptomolgy and the PCP (phencyclidine) model of schizophrenia.
  29. (2001). Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity.
  30. (2009). paper pending published: 23
  31. (1997). Parvalbumin-immunoreactive neurons are reduced in the prefrontal cortex of schizophrenics.
  32. (1989). Pathological-changes induced in cerebrocortical neurons by phencyclidine and related drugs.
  33. (1982). Phencyclidine (PCP): a review and perspectives.
  34. (2002). Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity.
  35. (1998). Schizophrenia and glutamatergic transmission.
  36. (1981). Sodium valproate enhancement of gamma-aminobutyric acid (GABA) inhibition: electro- physiological evidence for anticonvulsant activity.
  37. (2000). The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro.
  38. (2003). The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive defi cits in a reversal learning task in the rat.
  39. (1996). The behavioral and neurochemical effects of phencyclidine in humans and animals: some implications for modeling psychosis.
  40. (1998). The effects of MK-801 on aspartate and glutamate levels in anterior cingulate and retrosplenial cortices: an in vivo microdialysis study.
  41. (1999). The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia.
  42. (2003). The NMDA receptor hypofunction model of psychosis.
  43. (1989). Valproate enhances GABA turnover in the substantia nigra.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.