Sigma opioid receptor antagonists(University of Granada)

The hypothesis that postictal motor behaviors induced by a hippocampal afterdischarge (AD) are mediated by a pathway through the nucleus accumbens (NAC) and ventral pallidum (VP) was evaluated in freely moving rats. Tetanic stimulation of the hippocampal CA1 evoked an AD of 15-30 s and an increase in number of wet-dog shakes, face washes, rearings and locomotor activity. Bilateral injection of haloperidol (5 micrograms/side) or the selective dopamine D2 receptor antagonist, (+/-)-sulpiride (200 ng/side) before the hippocampal AD, into the NAC selectively reduced rearings and locomotor activity, but not the number of wet-dog shakes and face washes. Injection of R(+)-SCH-23390 (1 microgram/side), a D1 receptor antagonist, or rimcazole (0.4 mg/side), a sigma opioid receptor antagonist, into the NAC did not significantly alter postictal behaviors. Bilateral injection of muscimol (1 ng/side), a gamma-aminobutyric acid (GABAA) receptor agonist, into the VP before the AD significantly blocked all postictal behaviors. It is concluded that postictal locomotor activity induced by a hippocampal AD is mediated by activation of dopamine D2 receptors in the NAC and a pathway through the VP.