2-amino-7-phosphonoheptanoic acid, a selective N-methyl- d-aspartate antagonist, blocks swim-induced elevation of cerebellar cyclic guanosine monophosphate

Abstract

In order to explore how rapidly locomotor activity induces an elevation in cerebellar cyclic guanosine monophosphate (cGMP) content, Sprague-Dawley rats, pretrained to swim a 2.5-m 3ourse, were required to swim from one to 5 laps representing from 7 to 40 s of strenous activity. Immediately after completing the swimming task, each animal was killed by microwave irradiation and the cerebellum was collected for subsequent determination of the cGMP content. There was no difference in the cerebellar cGMP content between rats swimming one lap, i.e. for 7 s, and control rats that did not swim. However, there was a linear increase in the cGMP over control values from 1.8- to 2.4-fold in rats swimming 3 and 5 times, respectively. The first significant elevation of the cerebellar cGMP was seen at 24 s (3 laps). To determine if acidic amino acid pathways were involved in this elevation, a low dosage of a selective NMDA antagonist, 2-amino-7-phosphonoheptanoic acid (APH) was injected intracerebroventricularly 4 min before having rats swim 4 laps. This low dosage of APH, which alone had no effect on the cerebellar cGMP content, completely blocked the swim-induced elevation of this parameter. These data provide the first report of how quickly locomotor activity elevates the cerebellar cGMP content and further suggest that an NMDA receptor-mediated pathway is involved in the activity-induced elevation of this parameter.