Abstract:
RATIONALE:The synthetic progestin medroxyprogesterone acetate (MPA), widely used in hormone therapy (HT) and as the contraceptive Depo Provera, is implicated in detrimental cognitive effects in women. Recent evidence in aged ovariectomized (Ovx) rodents shows that short-term MPA treatment impairs cognition and alters the GABAergic system. OBJECTIVES:Using rats, we evaluated the long-lasting cognitive and GABAergic effects of MPA administered in young adulthood (Early-MPA), modeling contraception, and how this early exposure interacts with later MPA treatment (Late-MPA), modeling HT. METHODS:Early-MPA treatment involved weekly anti-ovulatory MPA injections (3.5 mg) from 4 to 8 months of age in ovary-intact rats. At 10 months old, rats were Ovx and weekly MPA injections were re-initiated and continued throughout testing for Late-MPA treatment. RESULTS:On the water radial-arm maze, all MPA-treated groups showed working memory impairment compared to Controls (p < 0.05); Early + Late-MPA rats were impaired on multiple dimensions of working memory (p < 0.05). On the Morris maze, Late-MPA rats showed greater overnight forgetting compared to Controls (p < 0.05). At study conclusion, MPA was detected in serum in all MPA-treated groups except Early-MPA, confirming treatment and clearance from serum in Early-MPA rats. In animals with detectable serum MPA, higher MPA levels were associated with less dorsal-hippocampal glutamic acid decarboxylase, the synthesizing enzyme for GABA (p = 0.0059). CONCLUSIONS:Findings suggest that MPA treatment leads to long-lasting cognitive impairments in the rodent, even in the absence of circulating MPA in animals given prior MPA treatment, which may relate to the GABAergic system. Further research defining the parameters of the negative impact of this widely used progestin on brain and cognition is warranted.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Braden BB,Garcia AN,Mennenga SE,Prokai L,Villa SR,Acosta JI,Lefort N,Simard AR,Bimonte-Nelson HAdoi
10.1007/s00213-011-2322-4subject
Has Abstractpub_date
2011-11-01 00:00:00pages
405-18issue
2eissn
0033-3158issn
1432-2072journal_volume
218pub_type
杂志文章abstract:RATIONALE:Schizophrenia is a disorder with cognitive deficits that could stem from cholinergic dysfunction. OBJECTIVES:Our aim was to examine if donepezil administered to stable, medicated outpatients with schizophrenia improves cognition and psychopathology. METHODS:We conducted a double-blind placebo-controlled tri...
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abstract::The effects of a new alpha-2 adrenoceptor antagonist on erectile function was assessed in 12 normal volunteers (mean age 28.7, range 20-42), using a double blind, placebo controlled design with two doses of drug and three testing sessions. The drug was administered by intravenous infusion and erectile responses to ero...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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