Dopamine and baclofen inhibit the hyperpolarization-activated cation current in rat ventral tegmental neurones

J Physiol. 1993 Mar:462:753-64. doi: 10.1113/jphysiol.1993.sp019580.

Abstract

1. Whole-cell patch-clamp recordings were made from dopamine-containing ventral tegmental area neurones in slices of rat midbrain. An inward current (Ih) was activated by hyperpolarization from -60 mV. 2. Dopamine (30 microM) reduced the amplitude of Ih 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 microM) also inhibited Ih; this action was antagonized by 2-hydroxysaclofen but not by (-)-sulpiride. The decrease in Ih 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 microM), forskolin (10 microM), the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine (100 microM), 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 GABAB receptors reduce Ih in ventral tegmental neurones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Baclofen / pharmacology*
  • Cations / metabolism
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Dopamine / pharmacology*
  • Electric Stimulation
  • Ion Pumps / drug effects*
  • Male
  • Membrane Potentials / physiology
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Potassium-Exchanging ATPase / drug effects
  • Tegmentum Mesencephali / metabolism*
  • Time Factors

Substances

  • Cations
  • Ion Pumps
  • Cyclic AMP
  • Sodium-Potassium-Exchanging ATPase
  • Baclofen
  • Dopamine