GABAB receptors in 5‐HT transporter‐ and 5‐HT1A receptor‐knock‐out mice: further evidence of a transduction pathway shared with 5‐HT1A receptors

Abstract

The functional properties of GABA_B receptors were examined in the dorsal raphe nucleus (DRN) and the hippocampus of knock‐out mice devoid of the 5‐HT transporter (5‐HTT–/–) or the 5‐HT_1A receptor (5‐HT_1A–/–). Electrophysiological recordings in brain slices showed that the GABA_B receptor agonist baclofen caused a lower hyperpolarization and neuronal firing inhibition of DRN 5‐HT cells in 5‐HTT–/– versus 5‐HTT+/+ mice. In addition, [³⁵S]GTP‐γ‐S binding induced by GABA_B receptor stimulation in the DRN was approximately 40% less in these mutants compared with wild‐type mice. In contrast, GABA_B receptors appeared functionally intact in the hippocampus of 5‐HTT–/–, and in both this area and the DRN of 5‐HT_1A‐knock‐out mice. The unique functional changes of DRN GABA_B receptors closely resembled those of 5‐HT_1A autoreceptors in 5‐HTT–/– mice, further supporting the idea that both receptor types are coupled to a common pool of G‐proteins in serotoninergic neurons.