Increased Density of Multiple-Head Dendritic Spines on Medium-Sized Spiny Neurons of the Striatum in Rats Reared in a Complex Environment

Comery, Thomas A.; Stamoudis, Catherine X.; Irwin, Scott A.; Greenough, William T.

doi:10.1006/nlme.1996.0049

Cited by 133 publications

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“…Previous reports indicate that environmental enrichment can produce structural, functional and biochemical modifications in neocortex and hippocampus (Jones et al, 1996;Kempermann et al, 1997). Environmental enrichment also has been found to increase neurogenesis, synaptic numbers, spine density, and growth factor expression in cortex and striatum (Comery et al, 1996;Jones et al, 1997;Pham et al, 1999;Segovia et al, 2006). Which one of these factors, if any, underline the enriched-induced increase in amphetamineinduced extracellular glutamate and aspartate levels in NAcc remains to be determined.…”

Section: Discussionmentioning

confidence: 96%

“…Enrichment has been shown to increase neurogenesis (Nilsson et al, 1999;Segovia et al, 2006), increase dendritic spines on medium size spiny neurons (Comery et al, 1996), increase synaptic density (Rampon et al, 2000) and increase the density of astrocytes (Pham et al, 1999). It is possible that these enrichment-induced modifications are associated with synaptic plasticity within the brain reward circuitry where glutamate neurotransmission plays a modulatory role (Wolf, 1998;Wolf and Xue, 1999;Giorgetti et al, 2001;Melendez et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Rahman

Bardo

2008

Brain Research

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In addition to dopamine (DA), evidence indicates that glutamatergic regulation of the mesolimbic reward pathway is involved in mediating the abuse-related effects of psychostimulants, including amphetamine. Since rats raised in an enrichment condition (EC) during development are more sensitive to the locomotor stimulant effects of acute amphetamine compared to rats raised in an impoverished condition (IC), the present study examined amphetamine-induced extracellullar glutamate and aspartate levels in the nucleus accumbens (NAcc) of EC and IC rats using in vivo microdialysis coupled with HPLC-electrochemical detection. Basal extracellular levels of glutamate or aspartate were not significantly different between EC and IC rats. Acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) increased extracellular glutamate levels in NAcc of EC rats (137% or 305% of basal) and IC rats (120% or 187% of basal). Similarly, acute systemic amphetamine (0.5 or 2.0 mg/kg, sc) elevated aspartate levels in NAcc of EC rats (148% or 237% of basal) and IC rats (115% or 170% of basal). Glutamate levels were elevated by amphetamine to a greater extent in EC rats than in IC rats. Pretreatment with systemic MK-801 (0.25 mg/kg, ip), a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, prevented the acute amphetamine-induced increase in extracellular glutamate and aspartate levels in NAcc. Overall, these results suggest that alterations in glutamate in the NAcc may be involved in the environment-dependent effects of amphetamine.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Rahman

Bardo

2008

Brain Research

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“…Indeed, we have found the regulation of three members of the Notch pathway, namely deltex homolog 3, embryonal stem cell specific gene 1 and dickkopf 2. Given the involvement of this pathway in cell fate and differentiation and in the regulation of neurite growth and adult neurogenesis (Berezovska et al, 1999;Costa et al, 2005), it is likely that these genes participate in the synaptic morphological changes induced by EE in the striatum (Comery et al, 1996;Kolb et al, 2003a,b). EE down-regulated the expression of several other genes that encode for proteins involved in cell structure such as synaptotagmin-like 4, Actinin alpha 3, Decorin, Actin alpha 2.…”

Section: Discussionmentioning

confidence: 99%

“…Altogether, these results support the proposition that EE induces a profound structural changes and reorganization of striatal neurons (Bezard et al, 2003;Nygren et al, 2006;Spires et al, 2004). For example, it has been shown EE induces long-lasting adaptations such as increases in spine density and arborisation in the striatum of rats (Comery et al, 1996;Kolb et al, 2003a,b). The striatum is one of the main terminals of dopamine neurons and it is a brain region that plays a pivotal role in drug addiction and in voluntary motor behaviour especially its dorsal part (Everitt and Robbins, 2005;Jaber et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

et al. 2008

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We have previously shown that environmental enrichment decreases the activating and rewarding effects of the psych psychostimulant cocaine and increases resistance to the neurotoxic effect of the Parkinson-inducing drug MPTP. These effects were accompanied by an increase in the striatal expression of the neurotrophin BDNF, an increase in the striatal levels of delta-Fos B and by a decrease in striatal levels of the dopamine transporter, the main molecular target for cocaine and MPTP. Here, we used cDNA arrays to investigate the effects of rearing mice in enriched environments from weaning to adulthood on the profile of expression of genes in the striatum focusing on genes involved in intracellular signalling and functioning. We found that mice reared in an enriched environment show several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and meta metabolism. Several of these findings were further confirmed by real-time quantitative PCR and, in the case of protein kinase C lambda, also by western blot. These findings are the first description of alterations in striatal gene expression by an enriched environment. The striatal gene expression regulation by environment that we report here may play a role in the resistance to the effects of drugs of abuse and dopaminergic neurotoxins previously reported.

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“…In a second analysis to examine the frequency of branched spines on nucleus accumbens cells, this procedure was repeated, but dendritic segments were drawn at 2000ϫ, and both total spines and spines with more than one head were counted. Branched spines were defined as described by Comery et al (1996), that is, spines with more than one head clearly connected to a common shaft. Thus, this analysis represents both a replication of the initial analysis, because different dendritic segments were drawn, and an extension to determine whether amphetamine had a disproportionate effect on the number of branched spines (i.e., those with multiple heads), as reported recently for rats raised in a complex environment (Comery et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine

1997

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Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (Ͼ1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.

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Increased Density of Multiple-Head Dendritic Spines on Medium-Sized Spiny Neurons of the Striatum in Rats Reared in a Complex Environment

Cited by 133 publications

References 0 publications

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

Environmental enrichment during adolescence regulates gene expression in the striatum of mice

Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine

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