Tani K, Iyo M, Matsumoto H, Kawai M, Suzuki K, Iwata Y et al. The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats. Br J Pharmacol 134: 1411-1418

Hamamatsu University School Of Medicine, Hamamatu, Shizuoka, Japan
British Journal of Pharmacology (Impact Factor: 4.84). 01/2009; 134(7):1411 - 1418. DOI: 10.1038/sj.bjp.0704370


We destroyed dentate granule cells unilaterally or bilaterally by means of intrahippocampal injection of colchicine in rats. Subsequently, we observed behavioural changes following the intraperitoneal injection of 2 mg kg−1 methamphetamine or saline, in addition to quantitatively assessing Fos protein expression in several brain regions, including the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus accumbens.
Bilaterally lesioned animals, when administered saline, showed a marked increase in locomotor activity compared with those of non-lesioned animals. With respect to the methamphetamine response, bilateral destruction resulted in a marked enhancement of locomotor activity, while the unilateral destruction led to a marked increase in rotation predominantly contralateral to the lesioned side, with no identifiable change in locomotor activity.
Bilaterally lesioned animals, when administered saline and having undergone an immunohistological examination, showed a marked increase in Fos expression in both sides of the nucleus accumbens. Bilaterally lesioned animals administered methamphetamine showed a marked increase in Fos expression in the right and left sides of all regions tested. Unilaterally lesioned animals administered methamphetamine showed a significant and bilateral enhancement in Fos expression in the medial prefrontal and cingulate cortices, and a marked and unilateral (ipsilateral to the lesioned side) enhancement of Fos protein in the piriform cortex, dorsal striatum, and nucleus accumbens.
The present findings suggest that dentate granule cells regulate methamphetamine-associated behavioural changes through the function of widespread areas of the brain, mostly the nucleus accumbens.
British Journal of Pharmacology (2001) 134, 1411–1418; doi:10.1038/sj.bjp.0704370

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Available from: Katsuaki Suzuki, Mar 21, 2014
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    • "This withdrawal-specific effect in LgA rats is worth noting because this maladaptive change could function to return the homeostasis of granule cell neuron turnover, or incubate drug, and drug-context associations relating to drug seeking (Vorel et al, 2001; Hiranita et al, 2006; Rademacher et al, 2006; Shen et al, 2006; Zhou and Zhu, 2006; Lasseter et al, 2010; Noonan et al, 2010; Luo et al, 2011). However, further functional exploration of this putative enhanced survival is warranted, as well as identification of other neuroadaptations during protracted withdrawal that may regulate the hippocampus and hippocampus-dependent relapse behavior (Tani et al, 2001; Hiranita et al, 2006; Zhou and Zhu, 2006; Lasseter et al, 2010; Noonan et al, 2010; Garcia-Fuster et al, 2011). We next determined whether relapse behaviors following noncontingent exposure to methamphetamine produces changes in dentate gyrus neural progenitors and whether these changes are altered compared with protracted withdrawal-induced changes. "
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