Activin A is increased in the nucleus accumbens following a cocaine binge

Wang, Zijun; Martin, Jennifer A.; Gancarz, Amy M.; Adank, Danielle N.; Sim, Fraser J.; Dietz, David M.

doi:10.1038/srep43658

Cited by 22 publications

(26 citation statements)

References 53 publications

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“…Relatively few studies have reported the effects of self-administered cocaine on properties of astrocytes. In addition to the report here and ( Scofield et al, 2016b ), a recent study found no effect on the number of GFAP-positive cells in the NAc core following a 12 h binge cocaine self-administration session, 14 days after the cessation of 10 days of cocaine self-administration ( Wang et al, 2017 ). It remains to be determined how long-access cocaine self-administration or punishment-resistant self-administration affects astrocyte structure and physiology.…”

Section: Discussionsupporting

confidence: 60%

Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction

Testen

Sepulveda-Orengo

Gaines

et al. 2018

Front. Cell. Neurosci.

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While much is known about the effects of cocaine use on the cellular structure and function of neurons and synapses within the brain’s reward circuitry, relatively little is known about the effects of cocaine on astrocytes. Given the significant role that astrocytes play in modulating neuronal and synaptic function, this lack of knowledge regarding the role of astroglial adaptations in the neuropathology of drug abuse represents an important investigative need. We recently showed that astrocytes within the nucleus accumbens (NAc) core exhibit decreased volume, surface area, and synaptic colocalization following cocaine self-administration and extinction, compared to NAc astrocytes from saline-administering animals (Scofield et al., 2016b). However, it is unknown whether these cocaine-dependent changes in astrocytes are ubiquitous throughout the brain’s reward circuitry, or represent specific adaptations within the NAc. It is also not known whether the extinction period is necessary for the retracted phenotype, or whether self-administration alone is sufficient to drive these changes. In the current study, we have extended our assessment of the effects of cocaine self-administration on morphometric properties and synaptic colocalization of astrocyte peripheral processes in the prelimbic region of the medial prefrontal cortex (PL) and basolateral nucleus of the amygdala (BLA), both known to also contribute significantly to motivated behaviors. In addition, in order to pinpoint the temporal dimension of previously observed effects, we also examined astrocytes within the NAc following the last self-administration session. While a reduction of astrocyte size and synaptic colocalization was observed in the NAc core of cocaine-extinguished rats as previously shown, no differences in PL or BLA astrocytes were observed between saline- and cocaine-extinguished rats. Moreover, decreased synaptic colocalization of peripheral processes in the NAc was observed with a post-synaptic marker, instead of a presynaptic marker as used previously. In contrast, no significant changes were found in NAc astrocytes after self-administration alone. These results provide insights into the influence of cocaine use on astrocytes within the brain reward circuitry, and inform both regional heterogeneity as well as temporal dynamics of astrocyte responsiveness to cocaine self-administration.

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Section: Discussionsupporting

confidence: 60%

Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction

Testen

Sepulveda-Orengo

Gaines

et al. 2018

Front. Cell. Neurosci.

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“…Methamphetamines induce activation of microglia in humans (9). Additionally, rodent models also support a role for microglial adaptation following COC administration (45).…”

Section: Discussionmentioning

confidence: 96%

Toll-like receptor 4 deficiency alters nucleus accumbens synaptic physiology and drug reward behavior

Kashima

Grueter

2017

Proc. Natl. Acad. Sci. U.S.A.

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Behavioral manifestations of drug-seeking behavior are causally linked to alterations of synaptic strength onto nucleus accumbens (NAc) medium spiny neurons (MSN). Although neuron-driven changes in physiology and behavior are well characterized, there is a lack of knowledge of the role of the immune system in mediating such effects. Toll-like receptor 4 (TLR4) is a pattern recognition molecule of the innate immune system, and evidence suggests that it modulates drug-related behavior. Using TLR4 knockout (TLR4.KO) mice, we show that TLR4 plays a role in NAc synaptic physiology and behavior. In addition to differences in the pharmacological profile of -methyl-d-aspartate receptors (NMDAR) in the NAc core, TLR4.KO animals exhibit a deficit in low-frequency stimulation-induced NMDAR-dependent long-term depression (LTD). Interestingly, the synaptic difference is region specific as no differences were found in excitatory synaptic properties in the NAc shell. Consistent with altered NAc LTD, TLR4.KO animals exhibit an attenuation in drug reward learning. Finally, we show that TLR4 in the NAc core is primarily expressed on microglia. These results suggest that TLR4 influences NAc MSN synaptic physiology and drug reward learning and behavior.

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“…Western blotting and immunofluorescent staining Western blotting and immunofluorescent staining were based on our previous studies with some modifications [21,28,29]. Primary antibodies used were as follows: anti-TAAR1 (1:500; Roche) or anti-GAPDH (1:2,000; CST, Boston, MA, USA), anti-c-Fos (1:500; Abcam, Cambridge, MA, USA) and either anti-NeuN (1:1,000; Millipore, Billerica, MA, USA), anti-GFAP (1:500; Millipore), or anti-IBA1 (1:500; Wako).…”

Section: Reinstatement Of Nicotine-seeking Behaviormentioning

confidence: 99%

Role of trace amine-associated receptor 1 in nicotine’s behavioral and neurochemical effects

Liu

Seaman

Siemian

et al. 2018

Neuropsychopharmacol

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Nicotine addiction and abuse remains a global health issue. To date, the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood. Trace amine-associated receptor 1 (TAAR1) is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictive-like behaviors. We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors. TAAR1 expression after nicotine treatment was evaluated by western blotting. c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release, respectively. We then thoroughly and systematically examined the role of TAAR1 in mediating nicotine-induced sensitization, nicotine discrimination, nicotine self-administration, nicotine demand curve, and the reinstatement of nicotine-seeking. Local pharmacological manipulation was conducted to determine the role of TAAR1 in the nucleus accumbens (NAcs) in the reinstatement of nicotine-seeking. We found that the expression of TAAR1 protein was selectively downregulated in the NAc, with no change in either dorsal striatum or prefrontal cortex. TAAR1 activation was sufficient to block nicotine-induced c-Fos expression in the NAc, while also reducing nicotine-induced dopamine release in the NAc. Systemic administration of TAAR1 agonists attenuated the expression and development of nicotine-induced sensitization, nicotine self-administration, the reinstatement of nicotine-seeking, and increased the elasticity of nicotine demand curve, while intra-NAc infusions of a TAAR1 agonist was sufficient to attenuate nicotine reinstatement. Moreover, TAAR1-knockout rats showed augmented cue-induced and drug-induced reinstatement of nicotine-seeking. These results indicated that modulation of TAAR1 activity regulates nicotine addictive-like behaviors and TAAR1 represents a novel target towards the treatment of nicotine addiction.

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Activin A is increased in the nucleus accumbens following a cocaine binge

Cited by 22 publications

References 53 publications

Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction

Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction

Toll-like receptor 4 deficiency alters nucleus accumbens synaptic physiology and drug reward behavior

Role of trace amine-associated receptor 1 in nicotine’s behavioral and neurochemical effects

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