Effects of hippocampal partial kindling on sensory and sensorimotor gating and methamphetamine-induced locomotion in kindling-prone and kindling-resistant rats

- Behavioral effects after partial hippocampal kindling (10 seizures) were studied.
- Seizure-prone rats showed sensorimotor and auditory gating deficits after kindling.
- Seizure-resistant rats showed methamphetamine-induced hyperlocomotion after kindling.
- GABAB receptor positive modulator reduced sensorimotor and auditory gating deficits.
- Dopamine antagonist haloperidol injected during kindling reduced the same deficits.

The effects of hippocampal partial kindling on gating of hippocampal auditory-evoked potentials (AEPs), prepulse inhibition (PPI) to an acoustic startle response, and methamphetamine-induced locomotion were examined in selectively bred kindling-prone (Fast) and kindling-resistant (Slow) rats. Ten electrographic seizures (afterdischarges, ADs) induced by high-frequency stimulation of the hippocampal CA1 region resulted in deficits in gating of hippocampal AEP and PPI in Fast, but not Slow, rats. The increase in AD duration with kindling was similar in Fast and Slow rats. Kindling-induced changes in hippocampal AEP and PPI in Fast rats were abolished by pretest injection of CGP7930 (1 mg/kg i.p.), a positive allosteric modulator of GABAB receptors. Injection of haloperidol (0.1 mg/kg i.p.) daily before kindling also prevented kindling-induced changes in PPI and hippocampal AEP in Fast rats. Interestingly, methamphetamine-induced hyperlocomotion was enhanced by kindling in Slow, but not Fast, rats. However, the methamphetamine-induced hyperlocomotion in Slow rats was not suppressed by daily injection of 0.1 mg/kg i.p. haloperidol before kindling, as compared with kindling without haloperidol. It is concluded that genetic disposition affected the behavioral consequences of repeated seizures. Fast rats required fewer hippocampal ADs to induce sensory (AEP) and sensorimotor (PPI) deficits, while Slow kindled rats were more sensitive to methamphetamine-induced locomotion. Dopaminergic blockade by haloperidol during kindling, or acute injection of CGP7930 before testing, attenuated some of the behavioral deficits induced by repeated hippocampal seizures, suggesting possible therapeutic strategies to treat the schizophrenic-like symptoms associated with temporal lobe epilepsy.