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There is increasing evidence that focal cerebral ischaemia produces remote functional alterations that may substantially contribute to the post-stroke neurological outcome. Changes initially limited to peri-infarct areas may evolve and spread via transneuronal connections to other structures. In the present study we investigated whether focal ischaemia produced by 2-h occlusion of the middle cerebral artery (MCAo) in SD rats may influence the physiological function of the hippocampus. Three days later in vitro long-term potentiation (LTP) was studied in hippocampal slices from ipsi- and contralateral hemispheres. In rats with MCAo LTP was not-inducible in the ipsilateral hippocampus, while the contralateral side expressed stable potentiation (6.6+/-4.1 vs. 35. 0+/-8.0%, respectively). Treatment with 6-h i.v. infusion of an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MRZ 2/579 starting at reperfusion not only preserved but additionally enhanced ipsilateral LTP, while a slight insignificant decrease was observed in the contralateral side (77.0+/-18.4 vs. 20.8+/-6.5%). The study demonstrates post-stroke functional changes in the hippocampus that can be modulated by NMDA receptor antagonists.

The aim of the present study was to investigate the influence of intrahippocampal neuropeptide Y (NPY) administration on the rats' behaviour. The CA1 field or dentate area (GD) of the dorsal hippocampus was chronically implanted with intracerebral cannulae. NPY (or redistilled water in the control group) was injected bilaterally or unilaterally in a volume of 1 microliter to each hippocampus, in a dose of 1 or 2 micrograms per rat. A separate group of rats was pretreated with amphetamine (1 mg/kg, s.c.), 15 min before a bilateral microinjection of NPY (2 micrograms) into the CA1 region. Immediately after the intrahippocampal injection, the rats' behaviour was tested in an open field box. It was found that NPY did not change the locomotor and the exploratory activity after either CA1 or GD administration to non-pretreated animals. In amphetamine pretreated rats, NPY injected into the CA1 field inhibited the amphetamine induced increase in sniffing and rearing and, to a lesser extent, the number of line-crossings. The obtained results may suggest an inhibitory action of NPY in the CA1 hippocampal field on the behavioural hyperactivity.

The effect of neuropeptide Y (NPY) on the picrotoxin-induced activity was studied in rat brain hippocampal slices in vitro and after intrahippocampal injection in vivo. In the hippocampal slices, NPY (0.1-0.5 microM) inhibited the picrotoxin-induced epileptiform activity recorded extracellularly in CA1 and CA3 hippocampal pyramidal cells. Similar inhibition was induced by the Y2 receptor agonist NPY13-36, which indicates that the effect of NPY was due to activation of Y2 receptors. In behavioural studies, rats with chronically implanted cannulae were injected unilaterally into the CA1 hippocampal region with a 1 ml volume of the studied substances. Picrotoxin in a dose of 1 mg (1.6 nmol) induced behavioural excitation, shakes and weak signs of epileptic behaviour. NPY in a dose of 2 mg (470 pmol), but not 1 mg, inhibited some excitatory effects of picrotoxin, but did not change the epileptic symptoms. The obtained results suggest that NPY has an inhibitory action in the hippocampus, which can be observed in vitro and also in a behavioural study.