Objectives: 

GH supplementation in rodents has been reported to ameliorate hippocampal-dependent cognitive deficits associated with normal aging (Esteban et al., Rejuv Res, 2010). As GH enhanced both AMPA- and NMDA-receptor–mediated excitatory postsynaptic potentials in hippocampal area CA1 (Mahmoud and Grover, J Neurophysiol, 2006), this work aims to study the acute effects of GH on working memory tasks in rodents and the possible involvement of AMPA and NMDA receptors and also MAP kinase signalling pathway.

Materials: 

To evaluate memory processes, two different tests were used, the spatial working memory 8-arm radial maze, and the novel object recognition as a form of non-spatial working memory test. Male Wistar rats were treated with saline or GH (2 mg/kg i.p.) 1 h before the tests. Different groups of rats were pre-treated with the AMPA antagonist DNQX (1 mg/kg i.p.) or NMDA antagonist MK801 (0.025 mg/kg i.p.) 10 min before the administration of GH. Also, the acute effect of MK801 and DNQX alone were analyzed.

Results: 

A significant improvement in memory processes were observed after GH administration in rats. Acute GH treatment improved spatial learning in the radial maze respect to the control group (26% reduction in the performance trial time, and 42% errors reduction) and increased (144%) the percent time exploring the novel object respect to the familiar object related to the control group. No significant changes were observed on working memory tasks after single administration of MK801 or DNQX at the mentioned doses. In rats pre-treated with MK801 or DNQX, the improving effects of GH on working memory tests were blocked. Moreover in mice, the MEK inhibitor SL 327 (20 mg/kg i.p.) blocked the positive effect of GH on radial maze.

Conclusions: 

In conclusion, GH improved working memory processes through both glutamatergic receptors AMPA and NMDA, probably by enhancing excitatory synaptic transmission in the hippocampus. These effects of GH required MAP kinase signalling pathway.