GABAB receptor GTP-binding is decreased in the prefrontal cortex but not the hippocampus of aged rats

Gamma aminobutyric acid (GABA)B receptors (GABABRs) have been linked to a wide range of physiological and cognitive processes and are of interest for treating a number of neurodegenerative and psychiatric disorders. As many of these diseases are associated with advanced age, it is important to understand how the normal aging process impacts GABABR expression and signaling. Thus, we investigated GABABR expression and function in the prefrontal cortex (PFC) and hippocampus of young and aged rats characterized in a spatial learning task. Baclofen-stimulated GTP-binding and GABABR1 and GABABR2 proteins were reduced in the prefrontal cortex of aged rats but these reductions were not associated with spatial learning abilities. In contrast, hippocampal GTP-binding was comparable between young and aged rats but reduced hippocampal GABABR1 expression was observed in aged rats with spatial learning impairment. These data demonstrate marked regional differences in GABABR complexes in the adult and aged brain and could have implications for both understanding the role of GABAergic processes in normal brain function and the development of putative interventions that target this system.