The aim of the current Etoposide mw study is to further investigate the possible interactions between antipsychotic treatment, estrogen and the dopaminergic system in a rodent
model, by using female, D-amphetamine sulphate (AMPH)-sensitized rats. Behaviors elicited by AMPH sensitization are thought to reflect some of the positive and cognitive symptoms of schizophrenia (Tenn et al., 2003; Featherstone et al., 2007). These changes are further thought to correspond to nucleus accumbens (NAcc) DA transmission changes in both rodents and non-human primates (Tenn et al., 2003; Castner et al., 2005; Peleg-Raibstein et al., 2008). In a previous study, locomotor activity was recorded in response to an acute injection of AMPH in male rats receiving chronic antipsychotic treatment over a period of 12 days (Samaha et al., 2007). Chronic continuous antipsychotic treatment became progressively ineffective at blocking AMPH-induced locomotion, with the higher doses resulting in a potentiated response to AMPH 5 days after treatment cessation. In the current study, we administered the typical antipsychotic haloperidol (HAL), at the lower concentration of the chronic regimen used by Samaha et al. (2007) which is still shown to reflect effective doses in humans (Kapur et al., 2000; Samaha et al., 2007, 2008) to either AMPH-sensitized or
non AMPH-sensitized female rats. Cetuximab clinical trial These ovariectomized (OVX) rats received either chronic low alone, or chronic low plus phasic high 17β-estradiol (E2) replacement to simulate two different estrogen levels during different phases of the estrous cycle in young females (Quinlan et al., 2008). Following an AMPH challenge, locomotor activity was recorded and NAcc DA and its metabolites were measured using in vivo microdialysis. It has been suggested that
antipsychotic administration may lead to DA receptor supersensitivity, which could lead to a almost rebound effect when drug administration is discontinued (Antelman et al., 1986; Samaha et al., 2008); such a rebound was observed in male rats following discontinuation of continuous HAL at a higher concentration than used here (Samaha et al., 2007). To examine this phenomenon in females, HAL administration was discontinued for 1 week, after which locomotor activity in response to an additional AMPH challenge was examined. Sixty-four female Sprague–Dawley rats (Charles River Laboratories, Montreal, QC, Canada) weighing 220–250 g were pair-housed and were the original N of this study. Cages were located in a 21 °C room with a 12-h reverse light–dark cycle (lights off at 09.00 h), with ad libitum access to food and water. Bedding consisted of a 50 : 50 mixture of corncob and beta-chip. All testing and surgical procedures were performed during the dark phase of the diurnal cycle.