Influence of opioids and naloxone on rhythmic motor activity in spinal cats

Abstract

The effects of L-DOPA, naloxone, and the opioids (D-Ala2,N-Me-Phe4,Gly5-ol)-enkephalin (DAGO) and D-Ser2-Leu-enkephalin-Thr6 (DSLET) on spinal motor rhythm generation were compared in anemically decapitated high spinal cats. After premedication with nialamide, DOPA caused the well-known, slow rhythmic motor activity with a locomotor pattern. The cycle duration of the evoked rhythm was usually between 3.9 and 5.0 s. The opioids DAGO and DSLET, injected intravenously (1.2-2 mg/kg) or suffused over the lumbar spinal cord (10(-3)-10(-4) M in Ringer's solution), severely depressed the DOPA-induced rhythmic activity, sometimes completely abolishing efferent motor activity. Naloxone (0.5-1 mg/kg i.v.) exerted different rhythm-facilitating effects, depending on the experimental condition. In the acute phase after spinalization, without paralysis and without nialamide and DOPA, naloxone induced rhythmic movements with a main frequency of 1.2-2 Hz. In the same preparation with paralysis, naloxone induced a rhythmic motor activity with a distinctly higher frequency (main range 4.3-5.8 Hz). After premedication with nialamide and DOPA, naloxone facilitated or, if a rhythm was absent, induced the slow-frequency DOPA type of rhythm. Given after i.v. or topical opioid application, naloxone antagonized the rhythm-depressing action of the opioid and caused an additional facilitation of rhythmic activity. Dopa and naloxone facilitated the long-latency, segmental reflex pathways from flexor reflex afferents (FRA), while the opioids depressed them. The short-latency FRA pathways were depressed by DOPA and opioids but were facilitated by naloxone. The influence of the different drugs on spinal motor rhythm generation is discussed in relation to their influence on short- and long-latency segmental pathways from FRA. If the rhythm generation induced by DOPA is based on the release of the long-latency FRA pathways, as has been proposed before, the rhythm-depressing action of opioids may be due to the suppression of these pathways, and the particular rhythm-generating function of naloxone may be related to its facilitation of short- and long-latency FRA pathways.