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.