Effects of chronic morphine and N6-cyclopentyl-adenosine administration on kainic acid-induced status epilepticus

Abstract

The aim of the present study was to investigate if the upregulation of μ or A 1 receptors modifies the expression of the kainic acid (KA)-induced status epilepticus (SE). Male Wistar rats received one of the following treatments: saline solution (SS) (1 ml/kg, i.p. for 7 days); morphine (M) (20 mg/kg, i.p. for 7 days) or N 6-cyclopentyl-adenosine (CPA) (1 mg/kg, i.p. for 9 days). Twenty-four hours after the last administration rats were sacrificed. Membranes were obtained μ and and A 1 receptor binding experiments were carried out. Furthermore, an injection of SS (1 ml/kg, i.p.) or KA (10 mg/kg, i.p.) was applied in rats pretreated chronically with M, CPA or SS, 48 h after the last administration. Seizure activity, death rate and a postictal explosive motor behavior were evaluated after KA administration. Chronic M administration increased μ receptor number in hippocampus (115%) and cortex (265%), whereas chronic CPA treatment enhanced A 1 receptor number in hippocampus (55%), amygdala (39%) and cortex (51%). The pretreatment with M facilitated the KA-induced SE and reduced the death rate as well as the postictal explosive motor behavior. The pretreatment with CPA delayed the SE presentation, increased the death rate and decreased the postictal explosive motor behavior. These findings suggest that upregulation of μ receptors enhances the KA seizures, whereas upregulation of A 1 receptors depresses these seizures.