Modulation of action of kainic acid on the behavior of rats by p-chlorophenylalanine and by gaba-mimetic drugs. Biochemical correlation between behavior and treatments.

Abstract

Systemic injection of kainic acid (KA, 11 mg/kg i.p.) to male albino Sprague-Dawley rats produced a sequence of behavioral events: stereotypies, convulsions, aphagia and aggressiveness in the form of sparring at artificial night fall, as well as a decline in brain-Gaba and brain-dopamine (DA)-levels followed by an increase in DA-levels on days 6 and 10 after treatment. No notable variations in serotonin (5-HT) was observed. Pretreatments of rats with GABA-mimetic drugs (gamma-vinyl GABA, 900 mg/kg i.p.; THIP, 1 microgram/1 microliter/rat, i.c.v.) prevented the occurrence of convulsion, aphagia and aggressiveness. Systemic injection of p-chlorophenylalanine (PCPA) (300 mg/kg i.p.) induced aggressiveness in the form of sparring at night fall. Treatment with PCPA followed by injection of KA shifted mild aggressive behavior to a violent one in the form of biting and killing familiar rats. The findings suggest that KA-neurotoxicity is due in part to its effects on GABA- and DA-neurotransmissions. It is shown also that convulsions are induced by a decline in GABA-level while sparring is provoked by an enhancement in DA-level. Violent aggressiveness is induced by the additive disruptive effects on GABA- and 5-HT-neurotransmissions in PCPA + KA treated animals.