EFFETTI CENTRALI DELLA TOSSINA TETANICA DIRETTAMENTA MICROINFUSA IN VARIE AREE CEREBRALI DI RATTO

The behavioural and electrocortical (ECoG) effects of intracerebral microinfusion of tetanus toxin in freely moving rats were studied. The microinjection into the III cerebral ventricle of tetanus toxin produced a dose-dependent behavioural stimulation accompanied by ECoG discharges. In fact, a dose of 240 MLD (for mice) produced, after a latency period of 48 h, an increase in locomotor activity circling and rolling, occasionally followed by tonic-clonic convulsions. Higher doses (500, 1000, 2500 and 5000 MLD) produced more marked behavioural and ECoG effects similar to those observed in rats microinjected into the hippocampus. A dose of 160 MLD was ineffective. The unilateral microinjection of tetanus toxin (250, 500, 2500 and 5000 MLD) into the hippocampus produced a dose-dependent picture of behavioural stimulation characterized by mioclonic movements of the limbs, circling, rolling and, occasionally, generalized tonic-clinic convulsions. These effects were more evident 24-48 h after the onset and were accompanied by ECoG epileptic discharges characterized by high voltage (300-400 μV) bouffes of bilateral spikes. Behavioural stimulation characterized by circling and rolling was elicited in rats which received tetanus toxin (2500 MLD) into the S. nigra (pars compacta). These effects were accompanied by ECoG epileptiform discharges. Similar behavioural and ECoG effects were observed after microinjection of tetanus toxin (500, 1000 and 2000 MLD) into the head of caudate nucleus. A pretreatment with drugs enhancing GABA-ergic transmission in the brain, i.e. sodium valproate (100 and 200 mg/kg 60 min before) given systemiccally, EOS (100 μg) or γ-vinyl-GABA (100 μg) given intracerebrally, reduced or completely antagonized although temporarily the behavioural and ECoG effects evoked by tetanus toxin given into the III cerebral ventricle or into specific areas of the rat brain. In addition the microinjection of F(ab)' (1.7 U.I./rat), a selective ligand for the neurotoxic chain of tetanus toxin, into the head of the caudate nucleus or into the lateral ventricle, was able to antogonize the behavioural and ECoG epileptiform effects evoked by previously microinfused tetanus toxin into the caudate nucleus.