Reciprocal innervation between serotonergic and GABAergic neurons in raphenuclei of the rat

Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The s lices were loaded with either [H-3] serotonin or [H-3]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA(A ) receptor agonist muscimol (3 to 30 muM) and the GABA(B) receptor agonist baclofen (30 and 100 muM) inhibited [H-3]serotonin and [H-3]GABA release. T hese effects of muscimol were reversed by the GABA(A) antagonists bicuculli ne (100 muM). The GABA(B) antagonist phaclofen (100 muM) also antagonized t he baclofen-induced inhibition of [H-3]serotonin and [H-3]GABA release. Pha clofen by itself increased [H-3]serotonin release but it did not alter [H-3 ]GABA overflow. Muscimol (10 muM) and baclofen (100 muM) also inhibited [H- 3]serotonin release after depletion of GABAergic neurons by isoniazid pretr eatment. These findings indicate the presence of postsynaptic GABA(A) and G ABA(B) receptors located on serotonergic neurons. The 5-HT1A receptor agoni st 8-OH-DPAT (0.01 to 1 muM) and the 5-HT1B receptor agonist CGS-12066A (0. 01 to 1 muM) inhibited the electrically stimulated [H-3]serotonin and [H-3] GABA release. The 5-HT1A antagonist WAY-100135 (1 muM) was without effect o n [H-3]serotonin and [H-3]GABA efflux by itself but it reversed the 8-OH-DP AT-induced transmitter release inhibition. During KCI (22 mM)-induced depol arization, tetrodotoxin (1 muM) did not alter the inhibitory effect of CGS- 12066A (1 muM) on [H-3]GABA release, it did blocked, however, the ability o f 8-OH-DPAT (1 muM) to reduce [H-3]GABA efflux. After depletion of raphe se rotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 muM) s till inhibited [H-3]GABA release whereas in serotonin-depleted slices, 8-OH -DPAT (1 muM) was without effect on the release. We conclude that reciproca l influence exists between serotonergic projection neurons and the GABAergi c interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT1A/B and GABA(A/B) receptors. Both synaptic and non-syna ptic neurotransmission may be operative in the 5-HTergic-GABAergic reciproc al interaction which may serve as a local tuning in the neural connection b etween cerebral cortex and midbrain raphe nuclei.