The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats - PubMed (original) (raw)

. 2001 Dec;134(7):1411-8.

doi: 10.1038/sj.bjp.0704370.

M Iyo, H Matsumoto, M Kawai, K Suzuki, Y Iwata, T Won, T Tsukamoto, Y Sekine, M Sakanoue, K Hashimoto, Y Ohashi, N Takei, N Mori

Affiliations

The effects of dentate granule cell destruction on behavioural activity and Fos protein expression induced by systemic methamphetamine in rats

K Tani et al. Br J Pharmacol. 2001 Dec.

Abstract

1. 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. 2. 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. 3. 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. 4. 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.

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Figures

Figure 1

Figure 1

Morphological effects of intrahippocampal colchicine (A) or saline (B). Coronal sections of the dorsal hippocampus stained with cresyl violet are shown. The granule cells are almost completely destroyed by colchicine (black arrowheads) (A). The white arrowheads show the insertion track of the cannulae used for injecting saline (B). The calibration bar is 500 μm.

Figure 2

Figure 2

Amount of locomotor activity after saline or methamphetamine administration in the C, BL, and UL group animals. The amount of locomotion in the BL group was significantly larger than that for the C (*P<0.001) and UL group (*P<0.001) after saline administration, while the latter two groups showed no significant difference (P_=0.88). After methamphetamine administration, the value for the BL group was markedly larger than that for the C (†_P<0.001) and UL group (†P<0.001), while there was no significant difference in locomotion between the latter two groups (_P_=0.23).

Figure 3

Figure 3

The induction of Fos protein in the dorsal striatum after saline (A) or methamphetamine administration (B), each from the BL group. The calibration bar is 100 μm.

Figure 4

Figure 4

The number of Fos-positive cells in the medial prefrontal cortex, cingulate cortex, piriform cortex, dorsal striatum, and nucleus accumbens following saline or methamphetamine administration. The white bars are for the left sides in the regions and the black bars are for the right sides. Error bars indicate s.e.mean. See also Tables 2A and B for post hoc pair comparisons.

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