Opposite modulatory effects of ovarian hormones on rat brain dopamine and serotonin transporters

Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 69978, Israel
Brain Research (Impact Factor: 2.83). 06/1997; 756(1-2):153-159. DOI: 10.1016/S0006-8993(97)00136-4

ABSTRACT The present study was designed to investigate the modulatory effect of gonadal steroids on brain dopamine (DA) and serotonin (5-HT) presynaptic transporters in female and male rats. Female and male rats were castrated and treated with either vehicle or gonadal hormones. The pharmacodynamic characteristics of the DA and 5-HT transporters were analyzed by [3H]BTCP and [3H]imipramine binding respectively. Ovariectomy (OVX) resulted in an upregulation of the striatal DA transporter and this alteration was prevented by estradiol (E2) or E2+progesterone (P) treatment but not by P alone. In contrast to the DA transporter, the hypothalamic 5-HT transporter was down-regulated by OVX in female rats and this decrease was reversed by the administration of E2, P or their combination. The striatal DA transporter and the hypothalamic 5-HT transporter in male rat were not affected by orchidectomy or by administration of testicular hormone. Our findings indicate that ovarian, but not testicular, steroid hormones may play an important role in the regulation of brain DA and 5-HT transporters. It appears that ovarian hormones modulate rat brain 5-HT and DA transporters in opposite directions. These interactions between ovarian steroids and presynaptic transporters may be relevant to DA- and 5-HT-related neuropsychiatric disorders.

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    • "Oestrogen and progesterone levels may also affect the actions of ecstasy, including the increased activity seen in female rats following MDMA. This has broad ramifications for sex differences in response to ecstasy, given that oestrogen levels affect the distribution and number of 5-HT and DA receptors (Sumner and Fink, 1995; Zhou et al., 2002) as well as the levels of serotonin (SERT) and dopamine (DAT) transporters in the brain (Attali et al., 1997), the actions of which underlie important physiological and psychological functions. Despite the evidence for sex differences in behavioural and physiological responses to ecstasy, there is uncertainty as to whether these translate into functional deficits (Allott and Redman, 2007). "
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    ABSTRACT: BACKGROUND: Ecstasy users report a number of adverse effects following use including mood and sleep disturbances. The present study examined differences in characteristics of ecstasy use (amount, frequency of use, reported harm resulting from use) between males and females and assessed relationships between ecstasy use, sleep quality and mental health outcomes. METHODS: An online survey of 268 ecstasy users (54.1% male, 45.9% female) was conducted. Validated sleep instruments assessing sleep quality and excessive daytime sleepiness, as well as questionnaires regarding physical and mental health (measured using the short-form health survey 12 (SF-12) and details of drug use were included. RESULTS: Male ecstasy users reported taking larger amounts of ecstasy, but were not more frequent users compared to females. Female ecstasy users were more likely to report increased harm following ecstasy including: feelings of guilt and remorse; failing to do what was normally expected of them; and having been told by others to cut down their ecstasy use. There were interactions between amount and gender and frequency and gender in predicting use of sleep medication and daytime dysfunction. There was a positive correlation between poorer sleep quality and negative mood, although this relationship was not moderated by sex. CONCLUSIONS: There is a significant association between sleep quality and mood disturbance in ecstasy users suggesting that these negative outcomes are co-morbid. These findings have implications for the treatment and advice given to ecstasy users who are experiencing sleep and/or mood related complaints.
    Drug and alcohol dependence 02/2013; 132(1-2). DOI:10.1016/j.drugalcdep.2013.02.002 · 3.28 Impact Factor
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    • "Further details in Murray et al. (2003). 1993a; Morissette and Di Paolo, 1993b), several lines of evidence in vivo and in vitro demonstrate that estrogens down-regulate striatal DAT expression and attenuate dopamine uptake in females (Attali et al., 1997; Disshon and Dluzen, 1999; Thompson, 1999). Together with the evidence discussed above that estrogen reduces neurotoxininduced striatal dopamine loss in females, these findings support the notion that suppression of DAT by estrogen at the time of neuronal insult is an important mechanism which contributes to the neuroprotective effects of this hormone (Dluzen and Horstink, 2003; McArthur et al., 2007b; Murray et al., 2003). "
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    ABSTRACT: This review considers evidence which reveals considerable complexity and sex differences in the response of the nigrostriatal dopaminergic (NSDA) system to hormonal influences. This pathway degenerates in Parkinson's disease (PD) and sex hormones contribute to sex differences in PD, where men fare worse than women. Here we discuss evidence from animal studies which allows us to hypothesize that, contrary to expectations, the acclaimed neuroprotective property of physiological concentrations of estradiol arises not by promoting NSDA neuron survival, but by targeting powerful adaptive responses in the surviving neurons, which restore striatal DA functionality until over 60% of neurons are lost. Estrogen generated locally in the NSDA region appears to promote these adaptive mechanisms in females and males to preserve striatal DA levels in the partially injured NSDA pathway. However, responses to systemic steroids differ between the sexes. In females there is general agreement that gonadal steroids and exogenous estradiol promote striatal adaptation in the partially injured NSDA pathway to protect against striatal DA loss. In contrast, the balance of evidence suggests that in males gonadal factors and exogenous estradiol have negligible or even harmful effects. Sex differences in the organization of NSDA-related circuitry may well account for these differences. Compensatory mechanisms and sexually dimorphic hard-wiring are therefore likely to represent important biological substrates for sex dimorphisms. As these processes may be targeted differentially by systemic steroids in males and females, further understanding of the underlying processes would provide valuable insights into the potential for hormone-based therapies in PD, which would need to be sex-specific. Alternatively, evidence that estrogen generated locally is protective in the injured male NSDA pathway indicates the great therapeutic potential of harnessing central steroid synthesis to ameliorate neurodegenerative disorders. A clearer understanding of the relative contributions and inter-relationships of central and systemic steroids within the NSDA system is an important goal for future studies.
    Hormones and Behavior 07/2009; 57(1):23-34. DOI:10.1016/j.yhbeh.2009.06.002 · 4.51 Impact Factor
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    • "This does not seem to be the case among humans exposed to famine; studies of the children born during and shortly after the Dutch Hunger Winter have not revealed any differences in age of first menstrual cycle, nor in a variety of other measures of reproductive function, with the exception of a small increase in perinatal deaths (Lumey and Stein 1997). Estradiol, a key hormone in the estrus cycle, is known to alter NMDA receptor binding and hippocampal CA1 dendritic spine density (Woolley 1998), DA transporter number (Attali et al 1997; Disshon et al 1998), D 2 receptors (Bazzett and Becker 1994), as well as to affect amphetamine-induced behaviors (Becker 1990; Becker and Beer 1986). Schizophrenia occurs in both men and women with women showing a somewhat later onset. "
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    ABSTRACT: Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.
    Brain Research 08/2008; 1237:62-74. DOI:10.1016/j.brainres.2008.07.089 · 2.83 Impact Factor
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