Cocaine selectively increases proliferation in the adult murine hippocampus

Abstract

Cocaine abuse continues to be a significant problem in the USA and elsewhere. Cocaine is an indirect agonist for dopamine, norepinephrine and serotonin with numerous potential downstream effects, including processes and signals associated with adult neurogenesis. Since drug addiction is associated with brain plasticity, we hypothesized that cocaine exposure would alter cellular proliferation in two adult neurogenic regions (the subventricular and subgranular zones). We used bromodeoxyuridine (BrdU) to track newly generated cells in the brains of adult mice after chronic cocaine or saline exposures. No differences were found in the number or migration patterns of BrdU-labeled cells in the forebrain neurogenic areas. However, cocaine produced a significant increase in the number of hippocampal BrdU-labeled cells. KeywordsCocaine; subventricular zone; subgranular zone; adult neurogenesis It is well documented that both short-term and chronic exposures to recreational drugs can induce structural changes in the brain [25,34], alterations in learning and memory [29], as well as changes in mood and cognition [2,39]. Although the mechanism underlying these changes is complex, alterations in neurogenesis may be a contributing factor [13]. The process of neurogenesis is well described in the adult nervous system [28]. It predominantly occurs in the dentate gyrus of the hippocampal formation and the subventricular zone (aSVZ) of the lateral ventricles, structures that are thought to contribute to memory formation, mood regulation and olfaction [44].A number of factors influence adult neurogenesis, including aging, stress, exercise, genes, the environment, and learning as well as circulating factors such as hormones, growth factors and neurotransmitters [44]. Neurogenesis in the subgranular zone of the adult hippocampus (SGZ) is decreased by corticosteroids [17] whereas antidepressant treatment results in increased proliferation and survival of newborn hippocampal cells, possibly through serotonin (5-HT) or norepinephrine-dependent mechanisms [43]. The monoamine

Chronic d-amphetamine administered from childhood to adulthood dose-dependently increases the survival of new neurons in the hippocampus of male C57BL/6J mice

“…On the other hand, some authors have found no effect (Mustroph et al, 2011) or increased neurogenesis from repeated cocaine treatment (Lloyd et al, 2010). Moreover, self-administration of methamphetamine for one hour, twice weekly for approximately 50 days increased numbers of immature neurons as indicated by DCX in rats (Mandyam et al, 2008).…”

Stress, stress hormones, and adult neurogenesis

“…Among these are neuropeptides, such as endogenous opioids and oxytocin and the neuromodulator dopamine. Some evidence suggests that each of these factors is capable of stimulating the production of new neurons in the hippocampus (Morton et al, 2009; Höglinger et al, 2004; Winner et al, 2009; Lloyd et al, 2010; Koehl et al, 2008; Persson et al, 2003). It is also possible that neurotrophic factors play a role in buffering the brain from the suppressive actions of elevated glucocorticoids.…”

Long-term effects of cocaine experience on neuroplasticity in the nucleus accumbens core of addiction-prone rats

“…In rodent models used to study addiction, repeated exposure to psychostimulants results in behavioral sensitization and accompanying neurobiological changes throughout the brain. Specifically, repeated cocaine exposure produces persistent changes in neuroplasticity, including dendritic remodeling (Robinson and Kolb, 1999, Robinson et al, 2001, Kolb et al, 2003, Li et al, 2004, Robinson and Kolb, 2004, Ferrario et al, 2005) and neurogenesis (Yamaguchi et al, 2004, Dominguez-Escriba et al, 2006, Garcia-Fuster et al, 2010, Lloyd et al, 2010, Noonan et al, 2010), that extend well beyond the period of active drug administration.…”