Sensorimotor Gating and Dopamine Function in Postpartum Rats

Abstract

There is much speculation regarding the effects of estrogen withdrawal at the end of pregnancy on forebrain dopamine, however, few studies have directly examine changes in this system postpartum. The present work sought to determine what changes in forebrain dopamine function occur in the postpartum rat. Specifically, prepulse inhibition of the acoustic startle response (PPI) was measured in primiparous female rats on postpartum day 2 (PPD2) or 14 (PPD14) following treatment with saline or the dopamine D2 agonist, quinpirole. Diestrus (DI) females served as controls. Dopamine content and turnover as well as cyclic AMP (cAMP) accumulation were determined within the nucleus accumbens and dorsal striatum in these same females. In addition, circulating levels of plasma corticosterone, estradiol and progesterone were measured. PPI was significantly disrupted in both postpartum groups. This effect was associated with decreased cAMP content within the nucleus accumbens. Quinpirole treatment (0.1 and 0.5 mg/kg) dose-dependently disrupted PPI in DI controls while PPD2 and PPD14 animals demonstrated reduced sensitivity to the D2 agonist. PPD14 animals demonstrated increased startle amplitude, an effect that was attenuated by quinpirole treatment. PPD14 females were also less sensitive to quinpirole-mediated reductions in DA turnover within the nucleus accumbens and both PPD2 and PPD14 females had an attenuated response to the stimulatory effects of quinpirole on corticosterone secretion. Collectively these findings suggest that the postpartum period is associated with reduced sensorimotor gating and altered forebrain DA systems, which may be related to shifts in circulating hormones.

Abrupt rather than gradual hormonal changes induce postpartum blues-like behavior in rats

“…Two studies reported that termination of pseudopregnancy, induced by injections with pregnant mare serum gonadotropin and human chorionic gonadotropin, caused anxiety-like behavior in the elevated plus which could be resolved by progesterone injections (Bitran and Smith, 2005;Bitran and Solano, 2005). In contrast to the above mentioned studies open field behavior in lactating rats did not differ from diestrous females at 2 days and 14 days postpartum (Byrnes et al, 2007). As the rats were lactating, the hormonal changes accompanying lactation might have opposed the anxiogenic effects of progesterone withdrawal, since anxiolytic effects of the lactation hormone oxytocin have been reported (Uvnas-Moberg, 1998).…”

“…In lactating rats a decrease in PPI has been reported. Furthermore, the startle amplitude was increased at the 14th but not on the 2nd day postpartum (Byrnes et al, 2007). In humans the startle response magnitude and PPI do not change during the first 3 postpartum days when compared to pregnancy.…”

“…PPI shows whether a non-startling pre-pulse reduces the startle response amplitude, and is a measure of sensorimotorgating. An increased ASR was found following P withdrawal (Gulinello et al, 2003) and in lactating rats (Byrnes et al, 2007). In pregnant women a decreased PPI was observed (Kask et al, 2008).…”

Genetic and neuroendocrine regulation of the postpartum brain

“…However, if one looks at the individual disorders, some possible connections are found. For example, in schizophrenia a dysregulation of sensory motor gating occurs (Braff and Geyer, 1990) and in mothers, changes in sensory motor gating also transpire (Byrnes et al, 2007). Thus, the same genes promoting alterations in sensory motor gating may be involved in both mothers and individuals with schizophrenia.…”

Patients with Premenstrual Dysphoric Disorder have Increased Startle Response Across both Cycle Phases and Lower Levels of Prepulse Inhibition During the Late Luteal Phase of the Menstrual Cycle

“…In addition to negative mood symptoms, objective manifestations of physiological arousal, such as the acoustic startle response, are also influenced by estradiol and progesterone (Byrnes et al, 2007;Toufexis et al, 1999;Vaillancourt et al, 2002;Van den Buuse and Eikelis, 2001). The acoustic startle response is increased in an animal model of PMDD , and was recently also shown to be increased in the luteal phase of PMDD patients (Epperson et al, 2007).…”