Repeated amphetamine administration induces Fos in prefrontal cortical neurons that project to the lateral hypothalamus but not the nucleus accumbens or basolateral amygdala

Department of Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
Psychopharmacology (Impact Factor: 3.88). 05/2008; 197(2):179-89. DOI: 10.1007/s00213-007-1021-7
Source: PubMed


The development of sensitization to amphetamine (AMPH) is dependent on increases in excitatory outflow from the medial prefrontal cortex (mPFC) to subcortical centers. These projections are clearly important for the progressive enhancement of the behavioral response during drug administration that persists through withdrawal.
The objective of this study was to identify the mPFC subcortical pathway(s) activated by a sensitizing regimen of AMPH.
Using retrograde labeling techniques, Fos activation was evaluated in the predominant projection pathways of the mPFC of sensitized rats after a challenge injection of AMPH.
There was a significant increase in Fos-immunoreactive cells in the mPFC, nucleus accumbens (NAc), basolateral amygdala (BLA), and lateral hypothalamus (LH) of rats treated repeatedly with AMPH when compared to vehicle-treated controls. The mPFC pyramidal neurons that project to the LH but not the NAc or BLA show a significant induction of Fos after repeated AMPH treatment. In addition, we found a dramatic increase in Fos-activated orexin neurons.
The LH, a region implicated in natural and drug reward processes, may play a role in the development and persistence of sensitization to repeated AMPH through its connections with the mPFC and possibly through its orexin neurons.

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Available from: Gloria Evelyn Meredith, Aug 18, 2014
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    • "The LH receives significant glutamatergic inputs from other brain regions such as the prefrontal cortex, lateral septum and basolateral amygdala. For example, Morshedi and Meredith (2008) have shown that a sensitizing regimen of amphetamine upregulates Fos immunoreactivity in medial prefrontal cortex neurons projecting to the LH. Further, cocaine CPP has also been demonstrated to produce increased Fos immunoreactivity in the lateral septum, another area that projects to the LH (Sartor and Aston-Jones, 2012). "
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    • "There is anatomic evidence showing reciprocal connections between the prefrontal cortex and the hypothalamus. For example, the MPFC sends inputs to the tuberal lateral hypothalamus (Gabbott, et al. 2005; Morshedi and Meredith 2008), a structure that is related to panic-like responses (Salgado- Rohner et al. 2011), in a region that is roughly coextensive with the ventromedial hypothalamic nucleus. In addition, although the projections from the DMH nucleus are mainly distributed into the MH (Thompson et al. 1996), some connections reach the medial division of the lateral hypothalamic area. "
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    • "However, repeated amphetamine does not enhance Fos labeling in mPFC-NAc or mPFC-basolateral amygdala neurons (Morshedi and Meredith, 2008), indicating that they comprise different populations than mPFC neurons containing BDNF. It is possible that that some BDNF-containing mPFC neurons activated by repeated amphetamine originate in the lateral hypothalamus, as Fos expression in mPFC neurons innervating this region are sensitized by amphetamine (Morshedi and Meredith, 2008). However, the VTA contains substantially more BDNFcontaining fibers than the lateral hypothalamus (Conner et al., 1997), and after amphetamine administration, more Fos-activated neurons innervating the VTA originate from the PFC than any other region (Colussi-Mas et al., 2007). "
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