The median and dorsal raphe nuclei (MR and DR, respectively) play an important role in behavioral inhibition. Inhibition of these regions disinhibits behavior: Administration of GABAergic agents such as muscimol and baclofen, serotonin 1A receptor agonists, or excitatory amino acid receptor antagonists into MR or DR are known to increase behavioral responses. Interestingly, administration of muscimol or baclofen into the MR or DR induces reward-related effects. We sought to determine whether administration of excitatory amino acid receptor antagonists into the MR or DR induces reward-like effects. Rats quickly learned to self-administer the AMPA receptor antagonist ZK 200775 into the vicinity of the MR, DR or medial oral pontine reticular nucleus, but not ventral tegmental area. Administration of the NMDA receptor antagonist AP-5 was not as effective as ZK 200775: AP-5 was self-administered into the MR, while it was not readily self-administered into other regions. In addition, noncontingent administration of ZK 200775 into the MR markedly increased responses rewarded by a salient sensory stimulus. While lever-pressing was increased by noncontingent administration of intra-MR ZK 200775 or contingent presentation of the stimulus, the magnitude of increase in lever-pressing with the presence of both intra-MR ZK 200775 and the stimulus was greater than the presence of either of them alone. These results suggest that the blockade of glutamate receptors, especially the AMPA receptors in the MR, is positively reinforcing and facilitates ongoing investigatory behavior. Glutamatergic afferents to the rostral raphe nuclei appear to play a role in tonic inhibition of reward-seeking processes.
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