Brainstem-mediated locomotion and myoclonic jerks. II Pharmacological effects.
Previous studies in our laboratory have demonstrated that microinjection of N-methyl-D-aspartate (NMDA) agonist into the nucleus magnocellularis (NMC) of the medial medulla increases muscle tone and/or produces locomotion, while injection of corticotropin-releasing factor (CRF) and non-NMDA agonists into the same or nearby sites suppresses muscle tone. In the first paper of this series, we report that myoclonic twitches or coordinated rhythmic leg movement (locomotion) can be induced by either NMDA or hemorrhagic bilateral lesion of the ventral mesopontine junction (vMPJ). In this paper, we report that microinjection of CRF (10 nM) or non-NMDA agonists, kainic acid (0.1-0.2 mM) and quisqualic acid (1-10 mM), into the NMC block locomotion and myoclonic twitches. The latency and duration of CRF and non-NMDA agonist-induced blockade of motor activity were short, at 34 s and 3.6 min, respectively. However, microinjection of the NMDA agonists DL-2-amino-5-phosphonovaleric acid (APV; 50 mM) or DL-2-amino-5-phosphonopentanoic acid (AP5, 20 mM) block myoclonus at a latency of 0.6-3 min with the block lasting for a mean of 7 h. Thus, activation of non-NMDA receptors or inactivation of NMDA receptors in NMC can block myoclonus. An imbalance between the inputs to these receptor systems may contribute to the generation of abnormal motor activation in waking and sleep.
Lai
Y Y
YY
VAMC, Sepulveda, CA 91343, USA.
Siegel
J M
JM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009207:Myoclonus / Q000503:physiopathology*; D016318:Quisqualic Acid / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D003346:Corticotropin-Releasing Hormone; D007608:Kainic Acid