Valproate prevents the induction and the expression of MK-801 sensitization.
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.
Yang
Pamela B
PB
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, PO Box 20708, Houston, TX 77225, USA.
Swann
Alan C
AC
Dafny
Nachum
N
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*
D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D016194:Receptors, N-Methyl-D-Aspartate; D014635:Valproic Acid; D016291:Dizocilpine Maleate