Alterations in the morphology of dendrites and dendritic spines in the nucleus accumbens and prefrontal cortex following repeated treatment with amphetamine or cocaine

Abstract

Repeated treatment with psychostimulant drugs produces changes in brain and behaviour that far outlast their initial neuropharmacological actions. The nature of persistent drug-induced neurobehavioural adaptations is of interest because they are thought to contribute to the development of dependence and addiction, and other forms of psychopathology, e.g. amphetamine psychosis. There are many reports that psychostimulants produce biochemical adaptations in brain monoamine systems, especially dopamine systems. The purpose of the present study was to determine if they might also alter the morphology of neurons in brain regions that receive monoaminergic innervation. Rats were given repeated injections of either amphetamine or cocaine, or, to control for general motor activity, allowed access to a running wheel. They were then left undisturbed for 24-25 days before their brains were processed for Golgi-Cox staining. Treatment with either amphetamine or cocaine (but not wheel running experience) increased the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the shell of the nucleus accumbens, and on apical dendrites of layer V pyramidal cells in the prefrontal cortex. Cocaine also increased dendritic branching and spine density on the basilar dendrites of pyramidal cells. In addition, both drugs doubled the incidence of branched spines on medium spiny neurons. It is suggested that some of the persistent neurobehavioural consequences of repeated exposure to psychostimulant drugs may be due to their ability to reorganize patterns of synaptic connectivity in the nucleus accumbens and prefrontal cortex.

Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5

“…This is the first evidence, however, suggesting that Cdk5 activity regulates the outgrowth and maintenance of spines in adult neurons in vivo. In addition, we report increased spine density in both NAc core and shell 1-2 days after 28-day cocaine exposure, whereas at 24-25 days post-treatment this effect was seen in the shell only (Robinson and Kolb, 1999;Robinson et al, 2001). …”

“…For example, repeated exposure to cocaine increases spine density on dendrites of dopaminoceptive medium spiny neurons in the shell (but not core) division of nucleus accumbens (NAc) (Robinson and Kolb, 1999;Robinson et al, 2001) and increases the expression of several transcription factors that mediate gene expression in these neurons (Nestler, 2001). Recently, cyclin-dependent kinase-5 (Cdk5) was identified as a downstream target of the transcription factor ΔFosB which is persistently expressed in NAc of mice repeatedly treated with cocaine.…”

Catechol O-Methyltransferase (COMT) mRNA Expression in the Dorsolateral Prefrontal Cortex of Patients with Schizophrenia

“…Thus, lower levels of pyramidal COMT mRNA in these external cortical layers may reflect this putative reduction of dendrites and/or spines, where COMT protein is presumably located, and may implicate catecholaminergic synapses as part of this process. In fact, studies in animals indicate that the activity of dopamine inputs to the prefrontal cortex directly covary with the density of spines (Robinson and Kolb, 1999).…”

Homers regulate drug-induced neuroplasticity: Implications for addiction

“…In all studies to date, both non-contingent and contingent cocaine or amphetamine administration were found to increase spine density, as well as dendritic branching on medium spiny GABAergic neurons within both the shell and core subregions of the NAC [198][199][200][201][202][203][204][205][206][207]. Similarly, repeated treatment with both psychomotor stimulants increase spine density and branching of the apical, and to a lesser extent the basalar, dendrites of glutamatergic pyramidal neurons within the PFC [198][199][200][201]204,205]. These structural data are consistent with greater levels of filamentous actin (Factin) within the NAC following both acute exposure to and withdrawal from repeated cocaine exposure [129].…”