Post-trial NMDA receptor allosteric blockade differentially influences habituation of behavioral responses to novelty in the rat.

The involvement of glutamatergic receptors of the N-methyl-D-aspartate (NMDA) type in long-term behavioral habituation (LTH) to a novel environment was investigated. To this aim, adult male Sprague-Dawley rats were first exposed to a Làt-maze. Horizontal (corner-crossings) and vertical activity (rearings) were measured per 1-min block. Immediately after a 10-min test trial in the maze, rats were systemically injected with either 6 or 20 mg/kg of the allosteric NMDA receptor blocker ketamine-HCl (KET) or vehicle. Retention was tested one week later. LTH was expressed as the decline in horizontal and vertical activity from test trial 1 to test trial 2. The results showed a facilitation of the two components of LTH at 6 mg/kg and a disruption at 20 mg/kg. This biphasic effect pertained to vertical activity only. For both activity components, the facilitation of LTH at 6 mg/kg pertained to the first part, whereas the inhibition at 20 mg/kg pertained to the second part of the testing period. Since horizontal and vertical activity are thought to have a prevailing cognitive (spatial) and non-cognitive (emotional) meaning, subanesthetic doses of KET differentially affect the long-lasting retention of these behavioral responses to novelty. Thus, NMDA receptors seem to be involved in the coupling of spatial and emotional components of information.