DOPAMINE AND BACLOFEN INHIBIT THE HYPERPOLARIZATION-ACTIVATED CATION CURRENT IN RAT VENTRAL TEGMENTAL NEURONS

1. Whole-cell patch-clamp recordings were made from dopamine-containing ventral tegmental area neurones in slices of rat midbrain. An inward current (I(h)) was activated by hyperpolarization from - 60 mV. 2. Dopamine (30 mum) reduced the amplitude of I(h) by 10-30 % at potentials from - 70 to - 120 mV. The effect was concentration dependent, mimicked by the D2 agonist quinpirole, and prevented by the D2 antagonist (-)-sulpiride. Baclofen (0.3-3 mum) also inhibited Ih; this action was antagonized by 2-hydroxysaclofen but not by (-)-sulpiride. The decrease in I(h) resulted from a reduction in the maximal current with no change in the voltage dependence. 3. The action of dopamine was unaffected by cadmium (200 mum), forskolin (10 mum), the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (100 mum), or by intracellular solution containing cyclic AMP (2 mm). 4. Ih was progressively reduced during the first 5-10 min of recording with electrodes containing guanosine 5'-O-(3-thiotriphosphate); after this time, dopamine had no further effect. 5. It is concluded that agonists acting at D2. receptors and GABA(B) receptors reduce I(h) in ventral tegmental neurones.