TABLE 1.

Studies of opioid and sedative effects in individual respiratory-related areas

Brain Region	Mu-Opioid Receptor	NMDA Receptor	GABAA Receptor
Carotid body	12, 78	65	65, 167
Nucleus tractus solitarii	30, 169	124
Retrotrapezoid nucleus	111	109	87, 155
Medullary raphe	168	10	87
Forebrain	105, 121, 125	93, 120	1, 60, 69, 119
Periaqueductal gray			138
Parabrachial Nucleus/Kölliker-Fuse Complex	3, 85, 103, 137, 160	40, 115	32, 35, 142
Pre-Bötzinger Complex	3, 107, 112, 145, 160	25, 113	15, 27, 98
Premotor neurons	57, 83, 149	80, 134	36, 100, 146, 148
Phrenic motoneurons	68, 149	100	100

Numbers correspond to reference numbers. Bold: where available, we quote “clinically relevant studies,” i.e., in vivo studies that record respiratory neuronal or global respiratory output during systemic drug application and localized antagonist injection or receptor deletion. Italic: if such studies are not available, we present in vivo studies recording respiratory-related neurons or global output during localized application of the sedative agent or the respective receptor agonist or antagonist at clinically relevant or higher concentrations; alternatively, these are descriptive studies using fMRI or EEG activity in humans. Roman: if no in vivo studies are available, we present in vitro studies using localized application of the receptor agonist/antagonist or indirect evidence. Sedatives included are NMDA receptor antagonists (e.g., ketamine) and GABA_A receptor agonists (e.g., Propofol and midazolam). Although clinically relevant opioid concentrations have been studied in vivo in many areas, this research still needs to be performed for clinically used sedatives.