title: Valproate prevents the induction and the expression of MK-801 sensitization.
abstract: Repeated administration of psychostimulants such as amphetamine, cocaine, and methylphenidate has been shown to induce behavioral sensitization. Sodium valproate, an anticonvulsant agent that enhances GABA activity, and dizocilpine (MK-801), a non-competitive NMDA receptor antagonist, can block the sensitization elicited by psychostimulants. MK-801 also has been demonstrated to sensitize to itself. The objective of the present study was to determine whether valproate disrupts the behavioral sensitization elicited by MK-801. Male Sprague-Dawley rats were given a regimen of repeated MK-801 injections (0.3 mg/kg, i.p.) that produced behavioral sensitization. They were also given valproate, at a dosage (50 mg/kg, i.p.) that prevented behavioral sensitization to stimulants, either during or after multiple MK-801 injections. After the washout period, animals were then re-challenged with MK-801 to determine whether valproate disrupted the behavioral sensitization elicited by MK-801. An activity monitoring system recorded horizontal activity, total distance, and vertical activity of the animals following drug treatment. Results of their locomotor responses demonstrated that valproate disrupted the development/induction and the expression of sensitization to MK-801, as it did to methylphenidate.
authors.affiliation: Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, PO Box 20708, Houston, TX 77225, USA.
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Yang
authors.forename: Alan C
authors.initials: AC
authors.lastname: Swann
authors.forename: Nachum
authors.initials: N
authors.lastname: Dafny
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018682:GABA Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013239:Stereotyped Behavior / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014635:Valproic Acid; D016291:Dizocilpine Maleate