Conditioned place aversion organized in the dorsal periaqueductal gray recruits the laterodorsal nucleus of the thalamus and the basolateral amygdala

The amygdala-ventral periaqueductal gray circuit is crucial for the expression of contextual conditioned fear. However, little is known about the neural circuits activated when the stimulation of the dorsal periaqueductal gray (dPAG) is used as unconditioned stimulus (US) in conditioned fear paradigms. The present paper examines the Fos-protein distribution in the brain of rats submitted to a conditioned place aversion (CPA) paradigm using the dPAG chemical stimulation with semicarbazide (SMC), an inhibitor of the GABA synthesizing enzyme, as US and the quadrant of an arena where the drug was injected as the paired neutral stimulus. Our results show that CPA associated with SMC injections caused a significant Fos labeling in the laterodorsal nucleus of the thalamus (LD), basolateral nucleus of amygdala (BLA) and in the dorsomedial PAG (dmPAG). This pattern of brain activation is clearly different from the neural substrates of the classical fear conditioning reported in the literature. Moreover, this paper shows that CPA with the use of chemical stimulation of the dPAG could be used as an experimental model of panic disorder with agoraphobia in the extent that panic attacks repeatedly associated with specific contexts may turn in this condition in the clinics. This condition activates the BLA probably through the LD. Besides, it indicates that the dPAG can be the link between amygdala and the brainstem motor regions that controls CPA when dPAG stimulation is used as US instead of footshocks. From this evidence we suggest that a loop dPAG-LD-BLA-dPAG is activated during the panic disorder with agoraphobia.