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Activation of 5‐HT1A and 5‐HT4(alpha) receptors differentially prevent opioid‐induced inhibition of brainstem cardiovascular and respiratory function
Author(s) -
Wang Xin,
Mendelowitz David
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a470-e
Subject(s) - gabaergic , neurotransmission , agonist , brainstem , opioid , pharmacology , medicine , fentanyl , endocrinology , inhibitory postsynaptic potential , anesthesia , neuroscience , receptor , biology
This study tests whether the cardiorespiratory inhibitory effects of opioids can be prevented by serotonin agonists. Respiratory activity and the inspiratory evoked GABAergic neurotransmission to cardiac vagal neurons (CVNs) in the nucleus ambiguus was studied in an in‐vitro brainstem slice preparation. The μ‐opioid agonist fentanyl inhibited respiratory frequency. The 5‐HT 1A receptor agonist, 8‐OH‐DPAT, increased respiratory frequency and also prevented the fentanyl induced respiratory depression. BIMU‐8, a 5‐HT 4α agonist, did not by itself change inspiratory activity but also prevented the μ‐opioid mediated respiratory depression. Fentanyl inhibited GABAergic neurotransmission to CVNs. 8‐OH‐DPAT inhibited spontaneous, but not inspiratory‐evoked GABAergic activity to CVNs. However 8‐OH‐DPAT prevented the opioid mediated depression of inspiratory evoked GABAergic activity, but did not change the opioid induced reduction in spontaneous GABAergic neurotransmission to CVNs. In contrast, BIMU‐8 did not alter GABAergic neurotransmission to CVNs by itself, but prevented the fentanyl depression of both spontaneous and inspiratory‐elicited GABAergic neurotransmission to CVNs. Activation of 5HT 4α receptors may be a useful therapeutic approach in preventing opioid evoked cardiorespiratory depression. Supported by a grant from the American Heart Association to X.W.