TY - JOUR
T1 - Nitric oxide synthase inhibition impairs delayed recall in mature monkeys
AU - Prendergast, Mark A.
AU - Terry, Alvin V.
AU - Jackson, William J.
AU - Buccafusco, Jerry J.
N1 - Funding Information:
The authors would like to thank Nancy Kille and Patricia Ryan for their excellent technical assistance. This study was supported by the Office of Research and Development, Medical Research Service of the Department of Veterans Affairs.
PY - 1996/1
Y1 - 1996/1
N2 - The gaseous neuromodulator nitric oxide (NO) is formed in brain regions known to mediate learning and memory processes. In rodent models, pharmacologic inhibition of NO synthesis impairs such processes. In the present study, N(ω)-nitro-L-arginine methyl ester (L-Name), an inhibitor of the constitutive form of the NO synthetic enzyme, was administered to seven non-aged, mature monkeys (Macaca Fascicularis, Macaca Mulatta, and Macaca Nemestrima) trained to perform a delayed matching-to-sample task (DMTS). L-Name (1,5, 25, and 50 mg/kg) produced marked decrements in task performance, as well as a reduction in the number of trials completed at the highest dose. This impairment of DMTS accuracy by the 50 mg/kg doses of L-Name appears to be associated with an aversive state marked by gastrointestinal disturbance and lethargy. The detrimental effects of the 25 mg/kg dose of L-Name on DMTS accuracy were completely blocked by concurrent administration of a mole-equivalent dose of the NO amino acid precursor L-arginine. As a whole, these data suggest that L-Name impairs processes involved in delayed recall in monkeys and that this impairment is associated with attenuated synthesis of NO. However, at higher doses (≤ 25 mg/kg) this impairment is associated with aversive effects of L-Name, possibly at both central and peripheral sites.
AB - The gaseous neuromodulator nitric oxide (NO) is formed in brain regions known to mediate learning and memory processes. In rodent models, pharmacologic inhibition of NO synthesis impairs such processes. In the present study, N(ω)-nitro-L-arginine methyl ester (L-Name), an inhibitor of the constitutive form of the NO synthetic enzyme, was administered to seven non-aged, mature monkeys (Macaca Fascicularis, Macaca Mulatta, and Macaca Nemestrima) trained to perform a delayed matching-to-sample task (DMTS). L-Name (1,5, 25, and 50 mg/kg) produced marked decrements in task performance, as well as a reduction in the number of trials completed at the highest dose. This impairment of DMTS accuracy by the 50 mg/kg doses of L-Name appears to be associated with an aversive state marked by gastrointestinal disturbance and lethargy. The detrimental effects of the 25 mg/kg dose of L-Name on DMTS accuracy were completely blocked by concurrent administration of a mole-equivalent dose of the NO amino acid precursor L-arginine. As a whole, these data suggest that L-Name impairs processes involved in delayed recall in monkeys and that this impairment is associated with attenuated synthesis of NO. However, at higher doses (≤ 25 mg/kg) this impairment is associated with aversive effects of L-Name, possibly at both central and peripheral sites.
KW - delayed matching
KW - learning and memory
KW - nitric oxide
KW - non-human primates
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U2 - 10.1016/S0091-3057(96)00160-8
DO - 10.1016/S0091-3057(96)00160-8
M3 - Article
C2 - 8981613
AN - SCOPUS:0031022422
SN - 0091-3057
VL - 56
SP - 81
EP - 87
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 1
ER -