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Maternal Programming of Defensive Responses 157Dopamine plays a critical modulatory role, optimizing the activity of mPFC neurons(Murphy et al., 1996; Williams & Goldman-Rakic, 1995). These functionsappear to be modified by postnatal maternal care through effects on genes thatinfluence extracellular dopamine signals in the mPFC.Prepulse inhibition (PPI) refers to the attenuation of an acoustic startle response(ASR) to a loud noise that is immediately preceded by a weaker acoustic stimulus(Geyer et al., 1990). PPI is sensitive to manipulations of mesocorticolimbic dopaminetransmission in the nucleus accumbens (Geyer et al., 1990, 2001; Swerdlowet al., 2001; Zhang et al., 2000) and mPFC (Bubser & Koch, 1994; Ellenbroeket al., 1999). The development of the mesocortical dopamine system and sensorygating, as measured by PPI, are sensitive to postnatal environmental conditions(Brake et al., 2004; Cilia et al., 2001; Ellenbroek et al., 1998; Le Pen & Moreau,2002; but also see Weiss et al., 2001).The offspring of Low LG-ABN mothers exhibit decreased PPI and show morepronounced, longer-lasting dopamine stress responses in the left mPFC comparedto the offspring of High LG-ABN mothers (Zhang et al., 2005). There are no differencesin the right mPFC dopamine response to stress. Both the prelimbic andinfralimbic areas of the mPFC are involved in the modulation of PPI. Nevertheless,the relationship between frontal dopamine activity and attention is not simple,with evidence that either deficits or excess dopamine produces attentional deficits(Arnsten, 2000). Nevertheless, the stress-induced increase in dopamine in theleft mPFC is 2–3 times higher than that in the offspring of High LG-ABN mothers,which would suggest the possibility of a dopamine-induced disruption of attentionand working memory.Recent findings from the Fleming lab support this idea. Lovic and Fleming(2004) found that as adults, pups reared artificially in complete absence of maternalcare show deficits in reversal learning, forming an attentional set (measuredby intradimensional shifts), and shifting attention (measured by extradimensionalshifts), with no deficits in simple and compound stimulus discriminations (Lovic& Fleming, 2004). In normally reared animals, this same pattern of behavior isproduced through lesions of either the prefrontal cortex or the hippocampus (Birrell& Brown, 2000; Li & Shao, 1998; Murray & Riddley, 1999). The effects of artificialrearing can be at least partially reversed during the first weeks of life byadditional tactile stimulation through stroking pups with an artist paintbrush, whichmimics the tactile stimulation afforded through licking/grooming by the rat mother.These findings are consistent with the idea that the tactile stimulation associatedwith maternal licking/grooming alters the mesocortical dopamine system andperformance on attentional tests.The increased dopamine response to stress in the offspring of Low LG-ABNmothers is accompanied by decreased mPFC expression of catechol-O-methyltransferase (COMT) by comparison to levels observed in samples from High-LGoffspring (Zhang et al., 2005). COMT is a postsynaptic enzyme that methylates