N. Galeotti et al., ROLE OF 5-HT4 RECEPTORS IN THE MOUSE PASSIVE-AVOIDANCE TEST, The Journal of pharmacology and experimental therapeutics, 286(3), 1998, pp. 1115-1121
The effects of the administration of different 5-HT4 receptor antagoni
sts (SDZ 205557, GR 125487) and 5-HT4 receptor agonists (BIMU 1, BIMU
8) on memory processes were evaluated in the mouse passive avoidance t
est. The administration of SDZ 205557 (10 mg kg(-1) i.p.) and GR 12548
7 (10 mg kg(-1) i.p.) immediately after termination of the training se
ssion produced an amnesic effect. BIMU 1 (20 mg kg(-1) i.p.) and BIMU
8 (30 mg kg(-1) i.p.), administered 20 min before the training session
, prevented the 5-HT4 receptor antagonist-induced amnesia. In the same
experimental conditions BIMU 1 (10 mg kg(-1) i.p.; 25 mu g/mouse intr
acerebroventricularly) and BIMU 8 (30 mg kg(-1) i.p.; 30 mu g per mous
e intracerebroventricularly) prevented scopolamine (1 mg kg(-1) i.p.)
and dicyclomine (2 mg kg(-1) i.p.) amnesia and, at the dose of 10 and
30 mg kg(-1) i.p. respectively, prevented amnesia induced by exposure
to a hypoxic environment. At the highest effective doses, none of the
drugs impaired motor coordination, as revealed by the rota rod test, o
r modified spontaneous motility and inspection activity, as revealed b
y the hole board and Animex tests. The 5-HT3 antagonist ondansetron (0
.1-1 mg kg(-1) i.p.) was unable to prevent scopolamine-, 5-HT4 antagon
ist- and hypoxia-induced amnesia. These results suggest that the modul
ation of 5-HT4 receptors plays an important role in the regulation of
memory processes. On these bases, the 5-HT4 receptor agonists could be
useful in the treatment of cognitive deficits although 5-HT4 receptor
antagonists may represent pharmacological tools for investigation of
new potential antiamnesic drugs.