Role of mitogen-activated protein kinases during recovery from head-shake response habituation in rats

Habituation is defined as a decrease in responsiveness to a repeatedly presented stimulus. The head-shake response (HSR) consists of a rapid twisting of the head about the front-to-rear axis elicited by a stream of air to the ear. This response demonstrates several fundamental properties of habituation including sensitivity to the frequency and intensity of stimulation, and spontaneous recovery. Despite an abundance of behavioral data on the HSR, relatively little is known about its physiological mechanism(s). To address this issue, changes in mitogen-activated protein kinases (MAPK) were assessed 5 min and 2, 6, and 24 h following the habituation of the HSR. Three cascades of MAPK activity were measured in the cerebellum and hippocampal, prefrontal, and piriform cortices, including extracellular-response kinase (ERK), p-38 kinase (p-38), and stress-activated protein kinase (SAPK). Significant activation of p-38 and SAPK was observed in all four brain structures, accompanied by modest changes in ERK activity. Recovery of the HSR was characterized by decreasing MAPK activation with control levels re-established 24 h after habituation. The present results suggest that MAPK activation mediates recovery from habituation; however, these findings may also support alternative interpretations such that MAPK activation reflects the encoding of spatial cues associated with the testing environment and/or are due to stress induced by the habituation protocol.