D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat.
نویسنده
چکیده
Opioids depress respiration and decrease chest wall compliance. A previous study in this laboratory showed that dopamine-D(1) receptor (D(1)R) agonists restored phrenic nerve activity after arrest by fentanyl in immobilized, mechanically ventilated cats. The reinstated phrenic nerve rhythm was slower than control, so it was not known whether D(1)R agonists can restore spontaneous breathing to levels that provide favorable alveolar gas exchange and blood oxygenation. It was also not known whether the agonists counteract opioid analgesia. In the present study, anesthetized, spontaneously breathing cats were given intravenous doses of fentanyl (18.0 +/- 3.4 microg/kg) that severely depressed depth and rate of respiration, lowered arterial hemoglobin oxygenation (HbO(2)), elevated end-tidal carbon dioxide (ETCO(2)), and abolished the nociceptive hind limb crossed-extensor reflex. Fentanyl (30 microg/kg) also evoked tonic discharges of caudal medullary expiratory neurons in paralyzed mechanically ventilated cats, which might explain decreased chest compliance. The selective D(1)R agonists 6-chloro APB (3 mg/kg) or dihydrexidine (DHD, 1 mg/kg) increased depth and rate of spontaneous breathing after opioid depression and returned HbO(2) and ETCO(2) to control levels. Opioid arrest of the nociceptive reflex remained intact. Pretreatment with DHD prevented significant depression of spontaneous breathing by fentanyl (17.5 +/- 4.3 microg/kg). Tonic firing evoked by fentanyl in expiratory neurons was converted to rhythmic respiratory discharges by DHD (1 mg/kg). The results suggest that D(1)R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia.
منابع مشابه
EFFECTS OF DOPAMINE RECEPTOR AGONISTS AND ANTAGONISTS ON BACLOFEN-INDUCED ANTINOCICEPTION IN FORM ALIN TEST
In this study, the influence of dopamine receptor agonists and antagonists on antinociception induced by bac10fen has been examined in the formalin test. The GABA-B agonist bac10fen induced antinociception in both phases of the formalin test in mice. The dopamine receptor agonists SKF 38393 and quinpirole also induced antinociception in both phases of the test. SKF 38393 but not quinpirole ...
متن کاملLateral hypothalamus chemical stimulation-induced antinociception was attenuated by injection of dopamine D1 and D2 receptor antagonists in the ventral tegmental area
Introduction: Stimulation or inactivation of the lateral hypothalamus (LH) produces antinociception. Studies showed a role for the ventral tegmental area (VTA) in the antinociception induced by LH chemical stimulation through the orexinergic receptors. In this study, we assessed the role of intra-VTA dopamine D1 and D2 receptors in antinociceptive effects of cholinergic agonist, carbachol, m...
متن کاملP139: Role of Dopamine Receptor D3 in Depression and Anxiety
Dopamine (DA) is one of the main catecholamines in the brain and is crucial for movement coordination, endocrine function, reward, mood, memory and emotions. The dopaminergic system is the primary therapeutic target in the treatment of Parkinson’s disease (PD), drug addiction and schizophrenia. Notwithstanding, dysfunction of central dopaminergic neurotransmission has also been associated to de...
متن کاملبررسی اثر و مکانیسم های اوپیوییدی و دوپامینرژیک دکسترومتورفان بر پاسخ درد ناشی از صفحه داغ در موش
Background and purpose : Dextromethorphan is a non-competitive NMDÂ receptor antagonist in the glutamatergic system with over 47 years of clinical usage experience as an over-the counter antitussive drug. We previously demonstrated that dextromethorphan modulates the pain threshold in the mouse acetic acid (0.6%,intraperitonealy)-induced writhing test (a tonic and chemical model for chronic p...
متن کاملThe Effects of Dopamine Receptor Agents on Swim Stress-Induced Inhibition of Naloxone-Induced Jumping Behavior in Morphine-Dependent Mice
In the present study, interactions of dopamine receptor agonists and antagonists with water swimming stress (WSS) on naloxone-induced jumping in morphine-dependent mice were examined. Mice were rendered dependent as described in the methods section. The opioid receptor antagonist, naloxone (1 mg/kg), was injected to elicit jumping (as a withdrawal sign). The first group exposed to WSS in the pr...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- American journal of physiology. Regulatory, integrative and comparative physiology
دوره 289 1 شماره
صفحات -
تاریخ انتشار 2005