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1. Intracellular recordings were made from 241 ventral tegmental neurones in slices of rat midbrain. Seventy-seven per cent of neurones were hyperpolarized by dopamine (principal cells); 16% were hyperpolarized by opioid peptides (secondary cells). 2. Most principal cells fired spontaneously (1-3 Hz) with a threshold of -53 mV; most secondary cells did not fire spontaneously. Action potentials of principal cells were longer (0.9 ms) than those of secondary cells (0.5 ms). 3. Focal electrical stimulation within the ventral tegmental area evoked a biphasic synaptic potential, depolarization followed by hyperpolarization, with a duration of about 200 ms. Experiments with receptor antagonists showed that the depolarizing component resulted from activation of both N-methyl-D-aspartate (NMDA) and non-NMDA receptors and the hyperpolarizing component resulted from activation of GABAA receptors. 4. A later hyperpolarizing synaptic potential developed after a latency of 50 ms, reached its peak in 250 ms and had a duration of about 1 s. It reversed polarity at -108 mV (external potassium concentration was 2.5 mM), was blocked by phaclofen (30 microM-1 mM) or 2-hydroxysaclofen (100-300 microM). In some cells, a phaclofen-resistant component remained that was increased by cocaine and blocked by sulpiride (1 microM). 5. It is concluded that the ventral tegmental area contains two types of neurone having properties similar to those in the substantia nigra. The cells receive synaptic inputs mediated by excitatory amino acids acting at NMDA and non-NMDA receptors, GABA acting at GABAA and GABAB receptors, and dopamine acting at D2 receptors.

The effects of agonists at mu and delta opioid receptors were compared by measuring membrane currents under voltage clamp from neurons of the rat nucleus locus coeruleus and guinea pig submucous plexus. In each tissue, the appropriate selective agonist (Tyr-D-Ala-Gly-MePhe-Gly-ol for mu receptors in locus coeruleus or Tyr-D-Pen-Gly-Phe-D-Pen for delta receptors in submucous plexus) increased the conductance of an inwardly rectifying potassium conductance and strongly hyperpolarized the membrane. The properties of the potassium conductance affected by the two opioids could not be distinguished. Experiments with intracellular application of guanosine 5'-[gamma-thio]triphosphate indicated that a guanine nucleotide-binding regulatory protein was involved in the coupling between opioid receptor and potassium channel, but there was no evidence for activation of either cAMP-dependent protein kinase or protein kinase C. It is noted that a number of vertebrate neurotransmitter receptors are coupled to potassium channels. The potassium conductance associated with these channels has properties similar to the conductance activated by mu and delta opioids; this family includes the following receptors: acetylcholine M2, norepinephrine alpha 2, dopamine D2, 5-hydroxytryptamine 5-HT1, adenosine A1, gamma-aminobutyric acid GABAB, and somatostatin. It is suggested that this conductance is a conserved neuronal effector coupled to one of the receptor types that mediates the effects of each of several major transmitters. The mu and delta opioid receptors appear to be unusual in that both utilize this same effector mechanism.