VALPROIC ACID-INDUCED RAPID CHANGES OF MET-ENKEPHALIN LEVELS IN RAT-BRAIN - PROBABLE ASSOCIATION WITH ABSTINENCE BEHAVIOR AND ANTICONVULSANT ACTIVITY

Valproic acid (VPA) induces abstinence behavior and analgesia and disp lays an anticonvulsant effect, but its exact mechanism of action is no t yet clear. In order to view whether proenkephalin derived-peptides a re involved in the mechanism of VPA-induced behavior, we analyzed immu noreactive-met-enkephalin (IR-ME) in rat striatum, midbrain, and amygd ala 10, 20, and 45 min after i.p. injection of 200 mg/kg of VPA. VPA i nduced body shakes that peaked within 5 to 10 min. IR-ME increased in the striatum and decreased in the midbrain at 10, 20, and 45 min, reac hing the highest and lowest levels at 10 and 20 min, respectively. No changes occurred in the amygdala. Gel filtration chromatography follow ed by HPLC of striatum extracts showed that the increased IR-ME levels corresponded to low molecular weight peptides, including ME. These re sults indicate that VPA produced rapid changes of IR-ME levels in rat brain and suggest peptide participation in the mechanisms of VPA-induc ed behavior. The anticonvulsant effect of VPA was tested in rats treat ed with pentylenetetrazol (70 mg/kg) 30 min after VPA (400 mg/kg) admi nistration, and IR-ME was analyzed in striatum 15 min later. No change s in striatal IR-ME levels occurred in protected rats (no behavioral c onvulsions), compared with those treated only with VPA, but a signific ant decrease appeared in unprotected animals (clonic convulsions). The se results suggest that striatal ME may participate in the mechanism o f VPA-induced abstinence behavior and in the anticonvulsant effect. Ot herwise, midbrain ME might be involved in other VPA behaviors such as analgesia.