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

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 71 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 identi®able 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 signi®cant 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 ®ndings suggest that dentate granule cells regulate methamphetamine-associated behavioural changes through the function of widespread areas of the brain, mostly the nucleus accumbens.

Levels of Neural Progenitors in the Hippocampus Predict Memory Impairment and Relapse to Drug Seeking as a Function of Excessive Methamphetamine Self-Administration

“…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).…”

“…With respect to methamphetamine addiction, a few reports have suggested that the hippocampus may contribute to specific aspects of methamphetamine addiction (Ursin et al, 1966;Ricoy and Martinez, 2009) and relapse (Tani et al, 2001;Hiranita et al, 2006;Shen et al, 2006;Rogers et al, 2008). Thus, it appears that plasticity in the hippocampus after chronic methamphetamine use may contribute to some of the addictive behaviors associated with chronic methamphetamine use.…”

Reduction of Adult Hippocampal Neurogenesis Confers Vulnerability in an Animal Model of Cocaine Addiction

“…Since lesions of the hippocampus produce hyperactivity (Emerich and Walsh, 1990; Tani et al, 2001; Hernandez-Rabaza et al, 2008) as well as increase perseverative lever pressing for both water and cocaine self-administration (Rabe and Haddad, 1968; Chambers and Self, 2002), we addressed the possibility that, like a hippocampal lesion, reduced neurogenesis via cranial irradiation might lead to hyperactivity and perseverative responding. Indeed, IRR-CSA rats pressed significantly more on the drug-paired left lever during the 15 sec timeout in the first two self-administration sessions (interaction of treatment and day, F 14,518 = 1.72, p<0.05; Figure 4A), suggesting greater cocaine intake during the first and second self-administration sessions is likely due to perseveration.…”

“…; Winocur et al, 2006; Wojtowicz and Kee, 2006; Airan et al, 2007; Wojtowicz et al, 2008), this paradigm maintains the integrity of mature hippocampal neurons while ablating neural progenitors. It did not grossly damage the dentate gyrus, as global hippocampal morphology and locomotion were not affected (Emerich and Walsh, 1990; Tani et al, 2001; Hernandez-Rabaza et al, 2008). This paradigm does not alter electrophysiological properties of mature hippocampal neurons or network dynamics (Snyder et al, 2005; Airan et al, 2007), suggesting that irradiation-induced alterations in hippocampal function are primarily due to the loss of adult-generated neurons (Wojtowicz, 2006).…”

Comprehensive behavioral assays to enhance phenotype to genotype linkages and therapeutic screening in mouse models of Down syndrome

“…The Ts65Dn mice also display higher overall locomotor activity, both in the home cage and a novel testing environment [19,[28][29][30]. It has been shown that prefrontal/hippo campal lesions in rodents can result in hyperactivity [40][41][42][43]. The pathological and chemical abnormalities in the prefrontal cortex and hippocampus [13], as well as altered cholinergic neurotransmission in Ts65Dn mice [10,44], may be responsible for this hyperactivity in Ts65Dn mice.…”