, 2004; Christianson et al., 2010) or both structures (Wu et al., 1999; Yang et al., 2008), Lino-de-Oliveira et al. (2002, 2006) showed that microinjections of glutamate into the DPAG reduce floating behavior whereas those of lidocaine had the opposite effect. Most importantly, the latter authors also showed that sub-chronic administrations of antidepressants reduce FST-induced increases in fos-like immunoreactivity in most columns of the PAG (Lino-de-Oliveira et al., 2002, 2006). Most notably, Natural Product Library however, recent data from positron-emission tomography

in rats (microPET) showed that whereas the PAG is markedly activated during FST training session, it remains inactive in test sessions (Jang et al., 2009). Lastly, plenty of evidence suggests that the protective effect of controllable stress is mediated by prefrontal cortex efferents to neurons of dorsal raphe (DR) which project to the DPAG (Maier Forskolin in vivo et al., 1995; Neumaier et al., 1997; Amat et al., 2005, 2006; Maier & Watkins, 2005; Rozeske et al., 2011). However, whereas the DR is the target of prefrontal cortex projections, predominantly inhibitory (Celada et al.,2001; Goncalves et al., 2009), the stimulation of DR either excites (directly) or inhibits (indirectly) the DPAG (Stezhka & Lovick, 1994). Moreover, DPAG levels of 5-HT did

not change either during exposure to IS (Amat et al., 1998) or 1 week thereafter (C.A. Rosa, unpublished results). Although the nature of DPAG-evoked freezing remains a matter of debate (De Oca et al., 1998; Schenberg et al., 2001, 2005; Vianna et al., 2001a,b), it is noteworthy that freezing was also markedly attenuated 1 week after exposure C59 research buy to IS. Consequently, the attenuation of DPAG-evoked escape behaviors cannot be ascribed to a facilitation of freezing at the

expense of trotting and galloping behaviors. Alternatively, the impairment of both passive (freezing) and active (flight) behaviors is best explained by the inhibition of a DPAG in-built motivational system. Therefore, rather than a ‘panicolytic effect’, the attenuation of elevated T-maze (De Paula Soares et al., 2011) and DPAG-evoked escape behaviors following the exposure to uncontrollable stress may be a reflection of a decrease in resilience to stress. This possibility is supported by the much greater attenuation of trotting and galloping, the responses most effective in one-way shuttle-box escape training, than of jumping. Strong et al. (2011) suggested, on the other hand, that 5-HT2C receptors of dorsal striatum (DS) play a crucial role in learning deficits of inescapably-shocked rats. In particular, whereas the microinjections of a 5-HT2C receptor antagonist into DS prevented the escape failure, microinjections of a respective agonist impaired learning even in the absence of prior exposure to IS. Accordingly, it is tempting to speculate that DPAG and DS mediate, respectively, motivational and learning aspects of helplessness.