Activation of nicotinic receptors on GABAergic amacrine cells in the rabbit retina indirectly stimulates dopamine release

The retina possesses subpopulations of amacrine cells, which utilize differ ent transmitters, including acetylcholine (ACh), GABA, and dopamine. We hav e examined interactions between these neurones by studying the effects of n icotinic agonists on GABA and dopamine release. Isolated rabbit retinas wer e incubated with [H-3]dopamine and then superfused. Fractions of the superf usate (2 min) were collected and the [H-3]dopamine in each sample was measu red. Endogenous GABA release was examined by incubating retinas in a small chamber. At 5-min intervals, the medium was changed and the GABA measured b y high-pressure liquid chromatography (HPLC). Exposure of the retina to nic otine, epibatidine, and other nicotinic agonists increased the release of b oth GABA and dopamine. The effects of nicotine and epibatidine were blocked by mecamylamine, confirming an action on nicotinic receptors. The action o f epibatidine on dopamine release was unaffected by glutamate antagonists b ut was blocked by picrotoxin and gabazine. Thc se results suggested that ni cotine might increase dopamine release indirectly by stimulating the releas e of GABA, which in turn inhibited the release of an inhibitory transmitter acting tonically on the dopaminergic amacrines. Exposure of the retina to GABA caused a small increase in dopamine release. This hypothetical inhibit ory transmitter was not GABA, an opioid, adenosine, glycine, nociceptin, a cannabinoid, or nitric oxide because appropriate antagonists did not affect the resting release of dopamine. However, metergoline, a 5HT(1)/5HT(2) rec eptor, antagonist, and ketanserin, a 5HT(2A) receptor antagonist, but not t he 5HT(1A) antagonist WAY 100635, increased the resting release of dopamine and blocked the effects of nicotine. The 5HT(1A)/5HT(7) agonist 8-hydroxy DPAT inhibited both the nicotine and GABA-evoked;ed release of dopamine. We conclude that nicotinic agonists directly stimulate the release of GABA, b ut the evoked release of dopamine is indirect, and arises from GABA inhibit ing the input of an inhibitory transmitter, which we tentatively identify a s serotonin.