Effects of chronic morphine and N-6-cyclopentyl-adenosine administration on kainic acid-induced status epilepticus

The aim of the present study was to investigate if the upregulation of mu o r A(1) receptors modifies the expression of the kainic acid (KA)-induced st atus epilepticus (SE). Male Wistar rats received one of the following treat ments: 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 sacrifi ced. Membranes were obtained mu and and A(1) receptor binding experiments w ere 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 post ictal explosive motor behavior were evaluated after KA administration. Chro nic M administration increased mu 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 wi th M facilitated the KA-induced SE and reduced the death rate as well as th e postictal explosive motor behavior. The pretreatment with CPA delayed the SE presentation, increased the death rate and decreased the postictal expl osive motor behavior. These findings suggest that upregulation of mu receptors enhances the KA se izures, whereas upregulation of A(1) receptors depresses these seizures. (C ) 2001 Elsevier Science B.V. All rights reserved.