Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: effects of 7-nitroindazole and zaprinast.
The effects of 7-nitroindazole, a putative selective inhibitor of neuronal nitric oxide (NO) synthase and zaprinast, a cGMP-selective phosphodiesterase inhibitor, were evaluated on recognition memory of rats in the object recognition test. This test is based on the differential exploration of a new and a familiar object. Two doses of 7-nitroindazole (10 and 30 mg/kg) and zaprinast (3 and 10 mg/kg) were used. The substances were administered i.p. immediately after the exposure to two identical objects, i.e., at the start of the delay interval. After a delay interval of 1 h, control rats spent more time exploring the new object which demonstrates that they recognized the familiar one. Both doses of 7-nitroindazole impaired the discrimination between the two objects after the 1 h interval. After a 4 h interval, control rats did not discriminate between the objects. The highest dose of zaprinast facilitated object recognition after the 4 h interval. In addition, this dose of zaprinast (10 mg/kg) reversed the recognition memory deficit induced by 7-nitroindazole (10 mg/kg) at the 1 h interval. The highest dose of 7-nitroindazole slightly increased mean arterial blood pressure 1 h after its administration. 4 h after administration of zaprinast (10 mg/kg), mean arterial blood pressure was also slightly increased, but not after 1 h after zaprinast administration. However, these effects on blood pressure do not explain the differential effects on object recognition memory. These results therefore suggest that NO-cGMP signal transduction is involved in object recognition memory independently of its cardiovascular role. Finally, since 7-nitroindazole affected mean arterial blood pressure it can not be regarded as a selective inhibitor of neuronal NO synthase.
Prickaerts
J
J
European Graduate School of Neuroscience EURON, Department of Psychiatry and Neuropsychology, Maastricht University, The Netherlands. jos.prickaerts@np.unimaas.nl
Steinbusch
H W
HW
Smits
J F
JF
de Vente
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000502:physiology*; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*
D007191:Indazoles; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C011145:zaprinast; D006152:Cyclic GMP; C080122:7-nitroindazole