TITLE:
Effects of Ovariectomy and 17β-Estradiol Replacement on Dopamine D2 Receptors in Female Rats: Consequences on Sucrose, Alcohol, Water Intakes and Body Weight
AUTHORS:
Abdoulaye Bâ, Seydou Silué, Brahima Bamba, Lociné Bamba, Serge-Vastien Gahié
KEYWORDS:
17β-Estradiol, Dopamine D2 Receptors, Bromocriptine, Sulpiride, Water, Sucrose, Alcohol Intakes, Obesity
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.8 No.1,
January
9,
2018
ABSTRACT: Background:
Mechanisms underlying overeating-induced obesity in post-menopausal woman include functional
lack of 17β-estradiol dysregulating dopamine
D2 receptors, thereby inducing food addiction, glucose craving or alcohol
dependence through reward circuitry. This study aimed at further understanding
17β-estradiol and dopamine D2
receptors interferences in the etiology of woman obesity. Method: Seventy-two Wistar female
rats weighing 200 - 205 g,
individually-housed, were divided into non-ovariectomized control (C = 6
groups) and ovariectomized rats (OVX = 6 groups) which were concurrently
subjected to the following treatments: Non-drug-treated (DMSO vehicle), 17β-estradiol (E2, 5 μg/kg, s.c.),
sulpiride (SUL, 20 mg/kg, i.p.), bromocriptine (BR, 0.1 mg/kg, i.p.), E2 + SUL or E2 + BR, designating the 6
constitutive groups of either control or ovariectomy. Within each experimental
group, consumption of different solutions (10% alcohol, 10% sucrose and water)
as well as food intake and body weight were daily measured, for 10
consecutive days. Results:
This study indicated that D2S was a specific inducer of alcohol and food
intakes, but reduced sugar consumption. In addition, 17β- estradiol
regulated the body weight set point, modulating D2S functions towards increased
food intake at lower weights and decreased food intake at higher weights. D2S
met the slow genomic actions induced by 17β-estradiol.
Conversely, D2L inhibited alcohol and food intakes, but induced specifically
sugar consumption, thereby regulating blood glucose levels and promoting energy
expenditure in reducing body weight. Indeed, 17β-estradiol exerted a tonic inhibition on D2L which was released by
OVX, exacerbating sugar intake and increasing body weight. D2L mediated the
rapid metabolic effects of 17β-estradiol. Conclusion: Our results
supported physiological data reporting that activation of the mostly expressed
presynaptically D2S-class autoreceptors decreased dopamine release stimulating
food intake, whereas activation of the predominantly postsynaptic isoform D2L
receptors increased dopamine activity inhibiting food intake. Our studies
indicated that 17β-estradiol acted on the
two types of D2 receptors showing opposite functions to equilibrate energy
intake vs. expenditure for weight set point regulation. Our data also supported
biochemical findings reporting that 17β-estradiol
induced D2 genes transcriptional regulation, thereby involving both types of D2
receptors in the etiology of obesity. The combined dysregulated effects of D2L
and D2S receptors, as 17β-estradiol
was lacking, would be causal factors underlying the etiology of obesity.