br Materials and methods br Results
Materials and methods
Discussion The 5-HT2A and D2 receptors have a functional crosstalk (Albizu et al., 2011) and they hcv protease inhibitors are all richly expressed in the mesolimbic and mesocortical systems (Azmitia and Segal, 1978; McMahon et al., 2001), providing the neuroanatomical basis for their interaction. The present study examined to what extent acute and repeated activation or blockade of 5-HT2A receptors modulates dopamine D2-mediated effects on pup preference and home-cage maternal behavior. After we validated the pup preference paradigm, we found that acute administration of TCB-2 and quinpirole suppressed pup preference mainly by decreasing the pup exploration time. In contrast, acute haloperidol injection had no effect (1.0 mg/kg) or even an opposite effect (0.05 mg/kg) on pup exploration. At 0.05 mg/kg, haloperidol selectively increased the pup exploration time without affecting the object exploration. MDL100907 had no effect on the pup and object exploration time and pup preference ratio. In the subsequent home-cage maternal behavior test, TCB-2, quinpirole and haloperidol all caused a similar disruption of active maternal responses, especially the pup retrieval. Once again, MDL100907 failed to alter any maternal response in the home cage. When used together, TCB-2 was found to enhance haloperidol's disruption of home-cage pup retrieval, but did not alter quinpirole's pup preference and home-cage maternal disruption (due to the floor effect). MDL100907 did not change quinpirole's disruption of pup preference and home-cage maternal behavior, nor haloperidol's maternal effects. These findings suggest that activation of 5-HT2A receptors (TCB-2) is capable of enhancing D2-mediated disruption of maternal performance, whereas blockade of 5-HT2A receptors (MDL100907) is less effective to alter D2 mediated maternal effects. They also indicate that 5-HT2A receptors may have a direct effect on maternal behavior independent of their interaction with D2 receptors. Naïve virgin female rats generally avoid infant rats, while mother rats are attracted to them and show a strong pup preference over other stimuli. Through maternal experience, mother rats develop strong social and emotional attachment towards the pups, as evidenced by the findings that they often increase their licking and nursing towards pups after a brief separation from their litters and exhibit depression-like behaviors if they experience a long period of repeated separation from their pups (Boccia et al., 2007). In the laboratory, the rewarding and reinforcing effect of pups has been investigated using the conditioned place preference (CPP) paradigm in which mother rats show a clear preference to a pup-associated environment over a neutral one after allowing several days of pup-mother interactions in the conditioning box (Fleming et al., 1994). In the present study, we used the pup preference test to assess this mother-infant bond (Olazabal et al., 2013). This test differs from the pup CPP, as it is a direct measure of emotional attachment towards pups, the so called “liking” aspect of maternal behavior (Berridge and Robinson, 2003) because it does not require any conditioning and any effort put forth by the mothers. We found that mother rats differed from virgins in their attractiveness to pups. Mothers tended to spend more time than virgin females on exploring the pup cage when they were tested with pups. When tested without pups, mother rats had similar amount of time exploring the cage as the virgins did. One drawback with the current setup is that the mother-virgin difference only appeared on the 1st test day and did not persist throughout the five-day testing period. This may be due to the unexpected higher intrinsic rewarding value of the cage (i.e., ~60% preference ratio even for the empty cage). In the future work, we will use two identical copies of the cage to see if the mother-virgin difference will persist throughout the postpartum period.