M. Gariboldi et al., STIMULATION OF 5-HT1A RECEPTORS IN THE DORSAL HIPPOCAMPUS AND INHIBITION OF LIMBIC SEIZURES INDUCED BY KAINIC ACID IN RATS, British Journal of Pharmacology, 119(5), 1996, pp. 813-818
1 We studied whether the stimulation of 5-HT1A receptors by 8-hydroxy-
2-(di-n-propylamino) tetralin (8-OH-DPAT), a specific 5-HT1A receptor
agonist, reduced electroencephalographic (EEG) seizures induced by int
rahippocampal injection of 0.04 mu g in 0.5 mu l of the glutamate anal
ogue kainic acid in freely-moving rats. 2 Pretreatment with 8-OH-DPAT
15 min earlier at the same site as kainic acid injection, caused a dos
e-dependent decrease of kainic acid-induced seizure activity. One and
10 mu g significantly reduced the total time spent in seizures by 72%
on average and the total number of seizures by 58% (P<0.01) and 43% (P
<0.05) respectively. The latency to onset of the first seizure was inc
reased 2.8 times (P<0.01) only after 1 mu g 8-OH-DPAT; 0.1 mu g was in
effective on all seizure parameters. 3 Systemic administration of 25,
100 and 1000 mu g kg(-1) 8-OH-DPAT significantly reduced the total num
ber of seizures and the total time in seizures induced by intrahippoca
mpal kainic acid by 52% and 74% on average. The latency to onset of th
e first seizure was delayed 1.8 times by 100 and 1000 mu g kg(-)1 (P<0
.05). 4 The anticonvulsant action of 8-OH-DPAT given intrahippocampall
y or systemically was significantly blocked by 5 mu g, but not 1 mu g
WAY 100635, a selective 5-HT1A receptor antagonist, administered in th
e hippocampus before the agonist. 5 These results indicate that postsy
naptic 5-HT1A receptors in the hippocampus mediate the anticonvulsant
action of 8-OH-DPAT and that their stimulation has an inhibitory role
in the generation of limbic seizures.