Sexually dimorphic effects of morphine and MK-801: sex steroid-dependent and -independent mechanisms.
Rats show gender differences in responses to morphine and the N-methyl-D-aspartate receptor antagonist dizocilpine (MK-801); the role of sex steroids in mediating these differences is unclear. We tested the overall hypothesis that circulating gonadal steroids determine the gender differences in morphine- and MK-801-induced behavior and c-Fos expression. Morphine caused a greater expression of c-Fos in the striatum of intact males than of that females, which was independent of sex steroids. MK-801 completely inhibited morphine-induced c-Fos in intact females but only caused partial inhibition in intact males; castrated males showed complete inhibition, which was reversed by testosterone, but gonadal steroids had no effect on this response in females. In thalamus, there was a large sex difference in the response to MK-801 that was independent of gonadal steroids. Behavioral responses to morphine were greater in males, but responses to MK-801 were greater in females; both were sex steroid independent. These findings show significant sex differences in response to morphine and MK-801 that are mediated by sex steroid-dependent and -independent mechanisms, which may be important in treatment outcomes of drug addiction.
D'Souza
Deborah N
DN
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Harlan
Richard E
RE
Garcia
Meredith M
MM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017781:Genes, Immediate-Early; D012739:Gonadal Steroid Hormones / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013788:Thalamus / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D012739:Gonadal Steroid Hormones; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D016291:Dizocilpine Maleate; D009020:Morphine