Excitatory neurotransmitters in the lateral habenula and pedunculopontine nucleus of rat modulate limbic seizures induced by pilocarpine

Abstract

The involvement of the excitatory neurotransmitter system in the lateral habenula and pedunculopontine nucleus in the initiation and propagation of limbic seizures induced by pilocarpine has been investigated in the rat. Limbic seizures occur in animals following bilateral microinjection into the lateral habenula of N-methyl-D-aspartate (NMDA) (5 and 12.5 nmol) or kainate (100 and 200 pmol), 15 min prior to a subconvulsant dose of pilocarpine (150 mg/kg, i.p.). In the absence of pilocarpine NMDA (5 and 12.5 nmol) or kainate (100 and 200 pmol), injected focally into the lateral habenula or pedunculopontine nucleus, produced sniffing, grooming and tremor but no electrographic or behavioural seizures. Limbic seizures also occur after a subconvulsant dose of pilocarpine when it is preceded by injection of NMDA (5 and 12.5 nmol) or kainate (50, 100 and 200 pmol) into the pedunculopontine nucleus. Behavioural and electrographic signs of limbic seizures following pilocarpine (380 mg/kg, i.p.) were attenuated or completely antagonized by focal injection into the lateral habenula of the NMDA antagonist, 2-amino-7-phosphonoheptanoate (AP7) (10 and 50 pmol) or kainate antagonist, gamma-D-glutamylaminomethylsulphonate (GAMS) (20 nmol). In addition, AP7 (0.05, 0.1 and 1.0 nmol) or GAMS (40 nmol) injected into the pedunculopontine nucleus suppressed limbic seizures induced by i.p. administration of pilocarpine (380 mg/kg). The relative efficacy of NMDA and non-NMDA receptor antagonists revealed that the selective NMDA antagonist, AP7, was more potent in its anticonvulsant activity in comparison to GAMS, a non-NMDA receptor antagonist.