The discrete localization of D3 receptors in the nucleus accumbens and subjacent islands of Calleja bears a close resemblance to the
dopamine-sensitive
anticonvulsant site in the anteroventral striatum. To determine if these D3 receptors were capable of attenuating limbic
motor seizures induced by
pilocarpine,
dopamine agonists with preferential or non-selective D3 affinity were injected stereotaxically into these limbic brain regions of the rat via indwelling
cannulae prior to
pilocarpine challenge. Reliable
clonic seizures were obtained by administering the proconvulsive
dopamine D1 agonist
SKF 38393 (10 mg/kg i.p.) followed by a subconvulsant dose of
pilocarpine (280-300 mg/kg i.p.). Bilateral intra-accumbens pretreatment with the D3 > D2 agonist
RU 24213 (0.2 pmol-7 nmol) significantly delayed the onset of
seizures, with a minimum effective dose of 2 pmol, without altering their frequency or severity. The more selective D3 agonist
LY 171555 (0.2 pmol-7.8 nmol) was less potent, and only attenuated
pilocarpine-induced
seizures at a dose (500 pmol) that would have stimulated accumbens D2 receptors as well. Intra-accumbens
injections of the highly potent and selective D3 agonist
7-OH-DPAT (20 pmol to 7 nmol) afforded no protection against
pilocarpine-induced
seizures.
Apomorphine, a mixed D1/D2/D3 agonist, delayed seizure onset at 100-500 pmol, but not at higher doses.
RU 24213,
LY 171555 and
7-OH-DPAT were all modestly
anticonvulsant when microinjected into the islands of Calleja at D2/D3 unselective doses. These data support the notion that
dopamine systems limit seizure propagation through the limbic forebrain, but suggest this protective effect is mediated by D2 rather than D3 receptors.