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    • Mother rats acutely treated with quinpirole and mg kg

    2021-07-31

    Mother rats acutely treated with quinpirole (0.5 and 1.0 mg/kg) decreased the pup exploration time but increased the object exploration, so they showed a significantly lower pup preference ratio. They also showed impaired maternal performance in the home cage, consistent with our previous study (Zhao and Li, 2010). Behaviorally, it is possible that quinpirole may have decreased the emotional processing of the rewarding value of pups and this suppression could explain quinpirole's effects in both tests. In a food-induced conditioned place preference test, Liu et al. (2008) reported that microinjections of quinpirole into the posteromedial VTA led to conditioned place aversion. Quinpirole administered to this site also decreased food intake and basal dopamine concentration in the ventromedial striatum. Based on the finding that quinpirole microinjected into the posteromedial VTA reduces dopamine cell firing (Beckstead et al., 2004; Olijslagers et al., 2004), they concluded that inhibition of midbrain dopamine neurons causes a negative affective state and disrupts positive affective encoding of food reward. The same could be said regarding pup reward. Quinpirole may have made mother rats aversive to pups, leading them to reduce their pup exploration time. This idea could be tested in a pup place preference test to see if quinpirole causes mother rats to develop a conditioned place aversion to the pup associated environment. Besides this possibility, quinpirole could also disrupt maternal behavior by impairing certain aspects of executive function, such as behavioral organization, attention and working memory, etc. Other studies have shown that D2 activation often causes perseverative responding, deficit in attention and working memory (Agnoli et al., 2013; Bushnell and Levin, 1993; Herold, 2010; Liu et al., 2008; Pezze et al., 2007; Wang et al., 2004). Under the influence of quinpirole, a mother rat might lose its ability to select and maintain appropriate behavioral responses in the presence of pups. Collectively, quinpirole may disrupt maternal behavior through at least two possible behavioral mechanisms targeting two different ARM1 areas. Quinpirole may cause a negative affect towards pups by acting on the D2 autoreceptors in the VTA (Liu et al., 2008), while it may disrupt executive functions necessary for normal maternal behavior by targeting the postsynaptic D2 receptors in the mPFC (Wang et al., 2004). Indeed, previous work does show that quinpirole significantly increases c-Fos expression in the mPFC, while it reduces c-Fos expression in the nucleus accumbens in postpartum female rats (Zhao and Li, 2010). Apparently, this intriguing idea needs to be rigorously tested in the future. Although haloperidol, like quinpirole, disrupted home-cage maternal behavior, it did not suppress pup preference. Haloperidol is well known for its suppression on maternal motivation (Giordano et al., 1990; Li et al., 2004; Silva et al., 2001; Stern and Keer, 1999; Zhao and Li, 2010). This idea is supported by extensive evidence showing that haloperidol-induced maternal disruption can be reduced to some extent by 4-h pup separation (Zhao and Li, 2009c); and haloperidol selectively suppresses behavioral measures indicative of maternal motivation (Stern and Keer, 1999; Yang et al., 2015). The dissociation between haloperidol's lack of effect on pup preference and its strong disruption of home-cage maternal behavior suggests that our pup preference test may not measure the motivational aspect of reward (pups) processing, especially the behavioral activation and effort-related aspects of maternal motivation (Salamone et al., 2016), but rather, measures the innate emotional aspect of reward processing and/or how a mother rat organizes its activities in response to two competing stimuli. These findings also suggest that a multi-test approach is often necessary to reveal the neurochemistry of specific psychological functions underlying maternal behavior. Although we were initially interested in how TCB-2 and MDL100907 alter the maternal effects of haloperidol, we also found that haloperidol reduced TCB-2-induced disruption of pup preference, indicating that blocking D2 receptors can also reduce 5-HT2A activation-induced maternal disruption. This action may be explained by haloperidol's inverse agonist action against 5-HT2A receptors (Weiner et al., 2001).