Inhibitory and excitatory effects of μ-, δ-, and κ-opioid receptor activation on breathing in awake turtles,Trachemys scripta

Abstract

Johnson SM, Kinney ME, Wiegel LM. Inhibitory and excitatory effects of -, ␦-, and -opioid receptor activation on breathing in awake turtles, Trachemys scripta. For ectothermic vertebrates, such as reptiles, the effects of opioid receptor subtype activation on breathing are poorly understood. On the basis of previous studies on mammals and lampreys, we hypothesized that -and ␦-opioid receptor (MOR and DOR, respectively) activation would cause respiratory depression, whereas -opioid receptor (KOR) activation would have no effect. To address this question, we measured respiration in awake, freely swimming adult red-eared slider turtles (Trachemys scripta) before and after injection with agonists for specific opioid receptors. Injection of the MOR agonist [D-Ala 2 ,NMe-Phe 4 ,Gly 5 -ol]-enkephalin acetate salt (DAMGO, 1.5 or 6.5 mg/ kg) decreased ventilation (V E) by 72 Ϯ 9% and 95 Ϯ 3%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in tidal volume (VT). DOR agonists, such as [D-Pen 2,5 ]-enkephalin hydrate (DPDPE, 5.0 mg/kg) and [D-Ala 2 ,DLeu 5 ]-enkephalin acetate salt (DADLE, 6.3 mg/kg), decreased V E by 44 Ϯ 10% and 89 Ϯ 4%, respectively, 4.0 h after injection as a result of decreased breathing frequency and no change in VT. DADLE also increased breath duration by a maximum of 25 Ϯ 9% at 6.0 h after injection. The KOR agonist U-50488 (6.2 mg/kg) increased VT by a maximum of 52 Ϯ 30% at 5.0 h after injection, with variable nonsignificant changes in V E and breathing frequency. Naloxone injections (0.25-0.5 mg/kg) 1.0 h before opioid agonist injections blocked all DAMGO-dependent effects, DPDPE-dependent frequency depression, and DADLE-dependent breath duration augmentation for 2.0 h after agonist injections. These results show that MOR and DOR activation causes respiratory depression as a result of decreased breathing frequency, whereas VT is increased after KOR activation.reptile; respiration; chelonian OPIOID DRUGS ARE COMMONLY administered in human and veterinary medicine to relieve pain, as well as reduce coughing, diarrhea, and anxiety. However, opioid drugs have deleterious side effects, such as respiratory depression, hypotension, nausea and vomiting, constipation, drowsiness, and physical dependence (18, 38). In mammals, opioid drugs can produce excitatory or inhibitory effects on breathing, depending on the drug, route of administration, presence of anesthesia, and species (42, 44). Even when specific opioid receptor agonists are microinjected into different parts of the ventral respiratory group (VRG) in the medulla of anesthetized rats, there are a variety of time-dependent changes in cardiorespiratory function, depending on the precise location of the injections (25, 26). Thus, understanding how opioid drugs alter respiration is important for development of effective drugs with fewer unwanted side effects.In ectothermic vertebrates, very little is known with respect to how opioid drugs modulate breathing. In intact frogs, morphine, a -, ␦-, and -opioid ...

Antinociceptive and respiratory effects following application of transdermal fentanyl patches and assessment of brain μ-opioid receptor mRNA expression in ball pythons

“…In intact red-eared slider turtles, injection of either a μ-opioid or δ-opioid receptor agonist drug decreases ventilation owing to a decrease in breath frequency with little change in tidal volume. 18 Similarly, bath application of either a μ-opioid or δ-opioid receptor agonist drug to isolated turtle brainstems spontaneously results in a respiratory motor pattern with a decrease in respiratory burst frequency in a concentration-dependent manner. 17,19 With respect to clinically relevant drugs, breathing frequency decreases following administration of morphine and butorphanol 11 and tramadol.…”

5-HT3 receptor-dependent modulation of respiratory burst frequency, regularity, and episodicity in isolated adult turtle brainstems

“…Likewise, the terrestrial tortoise ( Testudo graeca ) exhibits both singlet and episodic breathing, but the singlet breathing pattern is dominant (Gans and Hughes, 1967). For intact, semi-aquatic, red-eared slider turtles ( Trachemys scripta ) placed in water-filled tanks, the breathing pattern is mostly episodic with occasional singlets (Johnson and Creighton, 2005; Sladky et al , 2007; Johnson et al , 2008). To our knowledge, the breathing pattern of any chelonian on land versus in water has not been systematically studied, nor is it known whether 5-HT 3 receptor activation modulates breathing pattern in terrestrial or aquatic chelonians.…”

Regulation of respiratory-related hypoglossal motor output by α1 adrenergic and serotonin 5-HT3 receptor activation in isolated adult turtle brainstems

“…Likewise, relatively little is known regarding adrenergic modulation of respiratory burst clustering in vertebrates. In intact turtles, baseline respiratory events typically contain 4–6 breaths (Johnson et al ., 2008). In contrast, in isolated turtle brainstems, respiratory bursts occur in clusters of 1–7 bursts/respiratory event, with an average of 1.4 ± 0.4 bursts/respiratory event (Johnson and Creighton, 2005).…”