Morphine selectively depresses the slowest, NMDA-independent component of C-fibre-evoked synaptic activity in the rat spinal cord in vitro.
The effects of morphine on the depolarizing synaptic responses produced in motoneurons by electrical stimulation of primary sensory neurones have been recorded in hemisected spinal cord preparations (8- to 12-day-old rat pups). Morphine at concentrations of 0.1-20 microM reduced a slow, long-lasting (latency greater than 1 s, duration up to 10 s) component of the ventral root potential (VRP) evoked by C-fibre strength stimulation of the dorsal root. At 2 microM the reduction in area of this slow synaptic potential was 71.7 +/- 0.9% of control values (n = 15). The earliest components of the C-fibre strength VRP (the first 100 ms) and the responses to A beta strength stimuli were unaffected by the opioid even at 10-20 microM. The intermediate, NMDA receptor antagonist (D-AP5, 40 microM)-sensitive component (which lasts 100-1000 ms) was reduced by 34 +/- 2.2% of control (n = 15), which was significantly less than the reduction of the later NMDA-independent component (P < 0.001). Morphine (0.1-20 microM) also depressed the cumulative depolarization generated by the temporal summation of synaptic responses evoked by brief trains of C-fibre strength stimuli (1 or 10 Hz). A significantly greater reduction at the lower frequency of stimulation (56.3 +/- 2.0%) than at the higher (20.3 +/- 1.69%, n = 10, measured at 2 microM morphine) was found (P < 0.005). The effects of morphine were reversible upon wash-out or superfusion with the opioid receptor antagonist naloxone (2 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
Sivilotti
L G
LG
Department of Anatomy and Developmental Biology, University College London, UK.
Gerber
G
G
Rawat
B
B
Woolf
C J
CJ
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D009020:Morphine / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D009270:Naloxone; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine