Noradrenaline triggers GABAA inhibition of bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area.
The lateral part of the ventral bed nucleus of the stria terminalis (vlBNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the vlBNST after withdrawal from a 5d treatment with morphine. The vlBNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated alpha1-adrenergic receptors to increase GABA(A)-IPSC frequency. Noradrenaline produced a similar increase in GABA(A)-IPSCs during acute opioid withdrawal, but this increase resulted from activation of beta-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as alpha1-adrenergic receptors. Given that neurons in the vlBNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal.
Dumont
Eric C
EC
Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97239, USA.
Williams
John T
JT
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000096:biosynthesis; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009020:Morphine / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome; D017557:Ventral Tegmental Area / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009292:Narcotic Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D009020:Morphine; D004298:Dopamine; D009638:Norepinephrine