The dorsal midbrain anticonvulsant zone--III. Effects of efferent pathway transections on suppression of electroshock seizures and defence-like reactions produced by local injections of bicuculline.

Having provided an anatomical description of the efferent projections of the dorsal midbrain anticonvulsant zone [Shehab S. et al. (1995) Neuroscience 65, 681-695], our purpose in the present study was to establish which outputs from this region are responsible for mediating the anticonvulsant and behavioural properties of dorsal midbrain activation. The ability of unilateral injections of bicuculline into the dorsal midbrain anticonvulsant zone to suppress tonic hindlimb extension in the electroshock model of epilepsy was tested before and after three different knife cuts: (i) a transection of ipsilateral descending projections on the same side as the injection of bicuculline; (ii) an identical cut except it was placed contralateral to the injection; (iii) a cut which transected rostral projecting fibres from the dorsal midbrain anticonvulsant zone including most ipsilateral ascending and crossed descending projections. A fourth group of operated control animals was included to establish a baseline for the schedule of repeated testing. Qualitative observations of behaviour were taken immediately prior to administration of the electroshocks. Unilateral transection of ipsilateral descending efferents prevented the suppression of electroshock-induced hindlimb extension by injections of bicuculline into the dorsal midbrain anticonvulsant zone on the same side of the brain. Both the control cuts on the opposite side of the brain and the rostral cuts were ineffective. Transection of the ipsilateral descending projection on the same side as the injection of bicuculline also reduced the incidence of defensive reactions induced by the GABA antagonist, including explosive motor behaviour, oral attack and vocalization. Damage to this projection on the opposite side had little effect on the expression of behavioural reactions, neither did transection of the ascending efferents. These data suggest that ipsilateral descending efferents are critical for the suppression of electroshock-induced extension of the hindlimbs and the expression of defensive reactions elicited by activation of the dorsal midbrain.