Interactive effects of a protein kinase AII inhibitor and testosterone on spatial learning in the Morris water maze

Neurohormones such as testosterone (TE) are important in modulation of learning and memory. In the present study, we investigated the interactive effects of pre-training bilateral intra-hippocampal infusions of testosterone and H-89, a selective PKAII inhibitor, on spatial acquisition in the Morris water maze (MWM). Different doses of TE (20, 40 and 80 μg/side) and H-89 (5 and 10 μM/side) were administered 30 min before start of the training each day. Control animals received bilateral intra-hippocampal infusions of DMSO as vehicle for TE and H-89. Animals were trained for 4 days and each day included one block of four trials. The results of this study showed that bilateral infusion of TE (40 and 80 μg/side) or H-89 (10 μM/side) impaired spatial learning as indicated by significant increases in escape latency and traveled distance compared to the control group. Although pre-training bilateral infusions of a low concentration of either TE (20 μg/side) or H-89 (5 μM/side) into the CA1 region of the hippocampus did not affect learning capabilities, but the combination of the low doses of the drugs led to significant deficits in spatial acquisition. Overall, our data suggest that spatial acquisition was affected by PKAII inhibition or TE administration. Moreover, when co-administered, these drugs had a negative synergistic impact on acquisition.

► Intra-hippocampal infusion of 40 and 80 μg testosterone impaired spatial learning.
► Rats which received dose of 10 μM H-89 showed learning deficits.
► Intra-hippocampal infusion of either 20 μg testosterone or 5 μM H-89 did not cause spatial learning impairments.
► Deteriorations of learning capabilities were observed when a combination dose of the two compounds was administered.
► The effects on the cholinergic system and aromatase activity might be responsible for the combination group results.