Effects of nitric oxide synthase inhibitors on timing and short-term memory in rats

Nitric oxide synthase (NOS) inhibitors have been shown to affect the development of long-term potentiation and the acquisition of new learning. In the present study, we investigated the effects of NOS inhibitors in two animal models in which aspects of cognition are measured in well-learned operant tasks - a delayed non-match-to-position (DNMTP) task and a multiple signalled-unsignalled differential reinforcement of low rates (DRL) 15 s schedule - models of short-term memory and behavioral inhibition/timing, respectively. Since an overlap in the behavioral effects of NOS inhibitors and phencyclidine (PCP)-like N-methyl-D-aspartate (NMDA) antagonists has been observed previously, we compared our results with NOS inhibitors to those obtained with PCP. Whereas PCP produced a delay-independent decrease in the DNMTP task and increased burst responding (consecutive responses with inter-response intervals of < 3 s) in both the signalled and unsignalled components of the DRL procedure, 7-nitroindazole did not affect accuracy in the DNMTP task nor did it alter the pattern of responding in either component of the DRL schedule. Similarly, NG-nitro-L-arginine (L-NOARG) and NG-nitro-L-arginine-methyl-ester (L-NAME) did not affect accuracy in the DNMTP task. These results suggest that NOS inhibitors do not produce PCP-like disruption of behavioral inhibition or timing, nor do they decrease accuracy in a conditional discrimination task, as has been observed with PCP. The present results lend further support to the hypothesis that nitric oxide modulation does not affect retention of well-learned tasks, although it may affect acquisition of novel behavior.