Reduction of motor behavioural deficits in senescence via chronic prolactin or estrogen administration: time course and putative mechanisms of action.
The effects of chronic estrogen (E2), rat prolactin (rPRL), modified ovine prolactin (mPRL) administration on motor behavior (inclined screen performance) and striatal dopamine (DA) (D2subtype) receptor concentrations were examined in senescent (greater than 24 months of age) female rats, mPRL possesses no lactotrophic activity. Administration of either E2 or rPRL was effective in improving both inclined screen performance (increased time that the animal could remain on the screen by 95 and 413 s, respectively, compared to highest pre-injection performance) and striatal D2 receptor concentrations (14 and 20% respectively). These were indications, however, from separate analyses that improvements in inclined screen performance were seen prior to any increases in striatal D2 receptor concentrations. These early performance increases seemed instead to be the result of improved muscarinic receptor control over striatal DA autoreceptor function. Later improvements in inclined screen performance (at 6-7 days after the E2 injections were begun) were more dependent on increased striatal DA receptor concentrations. A second set of experiments which involved the injection of E2 into senescent male as well as female rats indicated that there were no sex differences in improvements in inclined screen performance, and that once the E2 injections were discontinued, performance returned to preadministration levels. The results are discussed in terms of two important processes that may be involved in mediating enhanced inclined screen performance following E2 administration: (1) enhancement of muscarinic receptor regulation of DA autoreceptor function; and (2) increases in striatal DA receptor density.
Joseph
J A
JA
Molecular Physiology and Genetics Section, Nia Francis Scott Key Medical Center, Baltimore, MD 21224.
Kochman
K
K
Roth
G S
GS
D000375:Aging / Q000502:physiology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010095:Oxotremorine / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D004967:Estrogens; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D010095:Oxotremorine; D011388:Prolactin; D004298:Dopamine