title: The medullary reticular formation is a site of muscle relaxant action of diazepam on deep back and neck muscles in the female rat.
abstract: We tested the hypothesis that the effect of systemic injections of diazepam (DZ, 125 mg/kg) to reduce the quality of the reproductive behavior, lordosis, and to reduce the EMG of lumbar back muscles involved in lordosis (Schwartz-Giblin et al., 1984) is exerted through a reticulospinal pathway with cells of origin in the nucleus gigantocellularis that excites lumbar motoneurons indirectly (Robbins et al., 1990, Robbins et al., 1992). In contrast, DZ facilitates lordosis behavior when infused into the midbrain central gray (McCarthy et al., 1995). Direct deposits of crystalline mixtures of DZ (20-80 ng) in dextrose were delivered to the medullary reticular formation (MRF) by diffusion from a cannula inserted through a guide to which a bipolar stimulating electrode was attached. The multiunit EMG response evoked by 20 (300 ms long) stimulus trains was recorded in back and neck muscles, lateral longissimus and splenius before and 5, 15, 30 and 60 min after local DZ deposits. There was a significant reduction in EMG response over this time period when stimulus intensities were within the range of 1.2-1.5 times threshold (Friedman two-way non-parametric test, P < 0.002). Large amplitude motor units that provide large tensions were the most sensitive to DZ-induced inhibition. Control deposits of dextrose had no significant effect. Systemic injections of progesterone (1 mg, i.p.) 60 min after DZ deposits, but not after dextrose deposits, further reduced the MRF-evoked EMG responses over the course of 1 h. As predicted, DZ infusions into the midbrain central gray did not reduce the reticulospinal-evoked axial muscle response, consistent with the facilitatory effect of midbrain central gray infusions of DZ on the lordosis quotient. The results suggest that benzodiazepine agonists (if endogenous) acting at sites in the MRF would be effective muscle relaxants during pregnancy, prior to the fall in progesterone that precedes labor.
authors.affiliation: Laboratory of Neurobiology and Behavior, Rockefeller University, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Schwartz-Giblin
authors.forename: M M
authors.initials: MM
authors.lastname: McCarthy
authors.forename: A
authors.initials: A
authors.lastname: Robbins
mesh_terms: D000818:Animals; D001415:Back; D003975:Diazepam / Q000494:pharmacology*; D004558:Electric Stimulation; D004576:Electromyography; D005947:Glucose / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008526:Medulla Oblongata / Q000502:physiology*; D008636:Mesencephalon; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D009334:Neck Muscles / Q000502:physiology*; D010487:Periaqueductal Gray / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects; D012154:Reticular Formation / Q000502:physiology*
chemical_list: D009125:Muscle Relaxants, Central; D011963:Receptors, GABA-A; D011374:Progesterone; D005947:Glucose; D003975:Diazepam