In vivo effects of estrogen and 2-hydroxyestradiol on D-2 dopamine receptor agonist affinity states in rat striatum

Abstract

The administration of estrogen to ovariectomized rats will result in a dopamine receptor hyposensitive phase at 24 hours followed within 48 hours by a hypersensitive phase. In an attempt to characterize further the molecular mechanism(s) which underlie this biphasic response, we studied the effects of estrogen and one of its metabolites (2-hydroxyestradiol) on striatal D-2 dopamine receptor agonist affinity states. Ovariectomized rats were treated daily with estradiol benzoate (EB; 10 micrograms/kg/day) for 3 days and sacrificed 24 hours after the last dose. Additional groups were treated with 2-hydroxyestradiol (2-OHE 2; 3 micrograms/kg/day), EB (100 micrograms/kg/day) or appropriate vehicle for 3 days and sacrificed 72 hours after the last injection. Animals sacrificed during the hyposensitive phase (i.e. 24 hours) displayed a significant decrease in the ratio of high/low agonist affinity states of the striatal D-2 receptor, while animals sacrificed during the EB- or 2-OHE 2-induced hypersensitive phase (i.e. 72 hours) showed no change in the ratio of high/low agonist affinity states.

Estrogen‐dependent alterations in D2/D3‐induced G protein activation in cocaine‐sensitized female rats

“…The dramatic reduction in D 2 /D 3 function within the dorsal and ventral STR correlated with higher levels of cocaine-induced rearing in OVX-EB rats, which may be partly attributed to a loss of D 2 /D 3 -mediated inhibition within these brain areas. Estrogen increases the expression of the D2L receptor isoform thereby affecting functional coupling to Gai/o proteins (Guiramand et al 1995), such as those interacting with D 2 /D 3 and endogenous opioid receptors (Clopton and Gordon 1986;Kelly and Wagner 1999). Cocaine, on the other hand, decreases pertussis toxin-sensitive G protein (Gai/o) in the NAc of male rats (Nestler et al 1990).…”

“…1990). Thus, it is possible that the contrasting effects of cocaine on D 2 /D 3 function observed in OVX and OVX‐EB rats may be due to the actions of cocaine and estrogen on Gαi/o protein coupling (Clopton and Gordon 1986; Maus et al . 1990; Steketee et al .…”

Effects of acute and chronic gonadectomy on the catecholamine innervation of the cerebral cortex in adult male rats: Insensitivity of axons immunoreactive for dopamine‐β‐hydroxylase to gonadal steroids, and differential sensitivity of axons immunoreactive for tyrosine hydroxylase to ovarian and testicular hormones

“…The literature describing estradiol's regulation of nigrostriatal dopamine systems in rats includes effects on nigral cell firing rates (Chiodo and Caggiula, 1983), transmitter levels or release (Becker and Ramirez, 1980;Becker, 1990;Castner et al, 1993), receptor binding (Clopton and Gordon, 1986;Falardeau and DiPaolo, 1987;Bazette and Becker, 1994), and dopamine-mediated motor behaviors (e.g., Gordon and Perry, 1983;Roy et al, 1990). For a majority of these, available evidence points to underlying mechanisms that utilize nongenomic means of hormone stimulation, including postulated hormone interactions with membrane-bound estrogen-binding proteins (see McEwen, 1991).…”

Neural mechanisms of reproduction in females as a predisposing factor for drug addiction

“…Similarly, estradiol potentiates D1 mediated neuronal excitability [47]. In contrast, D2 receptor binding is diminished with estradiol pretreatment [10,42,118], though the neurophysiological consequences of these receptor changes have not been tested. Again, these effects are transient and though they may contribute to the rewarding effects of drugs, they are unlikely to contribute to addiction vulnerability.…”