Behavioral effects and anatomic correlates after brain injury: a progesterone dose-response study.
Evidence suggests that progesterone enhances functional recovery in rats after medial frontal cortical contusions; however, a high dose of progesterone exacerbates tissue loss in a stroke model when administered chronically (7-10 days) prior to injury [Stroke 31 (2000) 1173)]. This study attempts to determine progesterone's dose-response effects on behavioral performance and GABA-A receptor expression following a cortical contusion. Male rats received injections of 0, 8, 16, or 32 mg/kg progesterone in 22.5% 2-hydroxypropyl-beta-cyclodextrin following cortical impact. Lesion 8 mg/kg and lesion 16 mg/kg groups displayed less thigmotaxis in the Morris water maze (MWM) than 0 and 32 mg/kg groups and were not significantly impaired relative to shams on other water maze measures. Increased variability in the 32 mg/kg group during somatosensory neglect testing was the only evidence indicating that a high dose of progesterone was disruptive to a few animals. These results suggest that low and moderate doses of progesterone are optimal for facilitating recovery of select behaviors and that postinjury progesterone treatment permits a wider dose range than preinjury treatment. Progesterone did not affect lesion size, but a strong negative correlation was observed between thalamic GABA-A receptor density and water maze performance. Future studies could explore causes for this relationship.
Department of Psychology, Emory University, Atlanta, GA 30322, USA.
Cynthia W
CW
Goss
Stuart W
SW
Hoffman
Donald G
DG
Stein
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000502:physiology; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D005552:Forelimb / Q000502:physiology; D007839:Functional Laterality / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010468:Perceptual Disorders / Q000523:psychology; D017397:Prefrontal Cortex / Q000293:injuries / Q000473:pathology; D011374:Progesterone / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology
D000893:Anti-Inflammatory Agents; D011963:Receptors, GABA-A; D011374:Progesterone