Activation of somatodendritic 5-HT sub(1A) autoreceptors in the median raphe nucleus disrupts the contextual conditioning in rats

We have shown that the median raphe nucleus (MRN) is involved in the control of contextual fear conditioning. Also, electrolytic lesion in the MRN causes signs of behavioral disinhibition, with an increase in locomotor activity measured in an open field. In this work, we have extended this study by analyzing the behavioral and autonomic responses in a contextual conditioning paradigm in rats with either neurochemical lesions from N-methyl-d-aspartate (NMDA), or microinjected with 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the MRN. The animals received NMDA, 8-OH-DPAT or saline microinjections into the MRN before the conditioning experiments, during which they were subjected to ten conditioning trials in an experimental chamber (same context) where they received foot-shocks (0.7 mA, 1 s with 20 s intervals). The next day, the animals were tested again either in the same or in a different experimental chamber, where the duration of freezing, number of rearings, bouts of micturition and number of fecal boli were recorded. Control rats placed in the same chamber showed more freezing than rats exposed to a different context. This freezing behavior was clearly inhibited in rats with NMDA lesions or with 8-OH-DPAT microinjections into the MRN. These MRN manipulations also produced a reduction in micturition. Such effects were context-specific since 8-OH-DPAT in MRN did not affect fear conditioned responses to tone previously associated with foot-shocks. In the open-field test, rats with neurotoxic lesions or with 8-OH-DPAT microinjections into the MRN had higher horizontal locomotor activity than control rats, without the number of rearings changing. As rats injected with 8-OH-DPAT into the MRN may freeze to a tone in a conditioned test paradigm and also show increased activity in an open field test the functional role of MRN on locomotor activity and contextual fear conditioning are clearly dissociated. Altogether, these results clearly show that such 5-HT mechanisms of the MRN serve as a neural substrate for the storage process of the context fear.