CM156, a sigma receptor ligand, reverses cocaine-induced place conditioning and transcriptional responses in the brain

Xu, Yan; Robson, Matthew J.; Szeszel-Fedorowicz, Wioletta; Patel, Divyen H.; Rooney, Robert J.; McCurdy, Christopher R.; Matsumoto, Rae R.

doi:10.1016/j.pbb.2011.12.016

Cited by 19 publications

(15 citation statements)

References 39 publications

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“…Total RNA was extracted from collected samples using Trizol (Invitrogen, Carlsbad, CA) as per manufacturer’s instructions. Reverse transcription and quantitative real-time PCR were conducted as previously described (Xu et al, 2012). TaqMan primers (Applied Biosystems, Foster City, CA) utilized for quantitative real-time PCR included: IL-1β (Mm00434228_m1), TSHb (Mm01308709_g1) and TRH (Mm01182425_g1).…”

Section: Methodsmentioning

confidence: 99%

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

Seminerio

Robson

McCurdy

et al. 2012

European Journal of Pharmacology

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Methamphetamine is currently one of the most widely abused drugs worldwide, with hyperthermia being a leading cause of death in methamphetamine overdose situations. Methamphetamine-induced hyperthermia involves a variety of cellular mechanisms, including increases in hypothalamic interleukin-1 beta (IL-1β) expression. Methamphetamine also interacts with sigma receptors and previous studies have shown that sigma receptor antagonists mitigate many of the behavioral and physiological effects of methamphetamine, including hyperthermia. The purpose of the current study was to determine if the attenuation of methamphetamine-induced hyperthermia by the sigma receptor antagonists, AZ66 and SN79, is associated with a concomitant attenuation of IL-1β mRNA expression, particularly in the hypothalamus. Methamphetamine produced doseand time-dependent increases in core body temperature and IL-1β mRNA expression in the hypothalamus, striatum, and cortex in male, Swiss Webster mice. Pretreatment with the sigma receptor antagonists, AZ66 and SN79, significantly attenuated methamphetamine-induced hyperthermia, but further potentiated IL-1β mRNA in the mouse hypothalamus when compared to animals treated with methamphetamine alone. These findings suggest sigma receptor antagonists attenuate methamphetamine-induced hyperthermia through a different mechanism from that involved in the modulation of hypothalamic IL-1β mRNA expression.

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Section: Methodsmentioning

confidence: 99%

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

Seminerio

Robson

McCurdy

et al. 2012

European Journal of Pharmacology

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“…Romieu et al, (2000, 2002, 2003) reported that the σR antagonists, NE 100, BD 1047 and progesterone blocked acquisition and expression of cocaine-induced place conditioning. Other σR antagonists reported to block place conditioning include the σ1 preferential antagonist, AC 927 (Matsumoto et al, 2011) and the slightly σ2 preferential antagonist, CM 156 (Xu et al, 2012). In addition, there is one report (Mori et al, 2014) that SA 4503, a σR agonist (Matsumoto, 2007) attenuates acquisition of place preference induced by morphine, cocaine and methamphetamine, whereas (+)-pentazocine was inactive, which begs the question of whether the effect was mediated by σRs.…”

Section: σR Ligands and Reinforcing Effects Of Stimulant Drugsmentioning

confidence: 99%

A role for sigma receptors in stimulant self-administration and addiction

Katz

Hong²,

Hiranita³

et al. 2016

Behavioural Pharmacology

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Sigma-1 receptors (σ1Rs) are structurally unique intracellular proteins that function as chaperones. σ1Rs translocate from the mitochondria-associated membrane to other sub-cellular compartments, and can influence a host of targets, including ion channels, G-protein-coupled receptors, lipids, and other signaling proteins. Drugs binding to σRs can induce or block the actions of σRs. Studies indicate that stimulant self-administration induces reinforcing effects of σR agonists, due to dopamine transporter actions. Once established the reinforcing effects of σR agonists are independent of dopaminergic mechanisms traditionally thought to be critical in the reinforcing effects of stimulants. Self-administered doses of σR agonists do not increase dopamine concentrations in the nucleus accumbens shell, a transmitter and brain region considered important for reinforcing effects of abused drugs. However, the self-administration of σR agonists is blocked by σR antagonists. Several effects of stimulants have been blocked by σR antagonists, including reinforcing effects assessed by a place-conditioning procedure. However, the self-administration of stimulants is largely unaffected by σR antagonists, indicating fundamental differences in the mechanisms underlying these two procedures used to assess reinforcing effects. When σR antagonists are administered in combination with dopamine uptake inhibitors an effective and specific blockade of stimulant self-administration is obtained. Actions of stimulant drugs related to their abuse induce unique changes in σR activity and the changes induced potentially create redundant, and once established, independent reinforcement pathways. Concomitant targeting of both dopaminergic pathways and σR proteins produces a selective antagonism of stimulant self-administration, suggesting new avenues for combination chemotherapies to specifically combat stimulant abuse.

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“…Further, the NAc has been implicated in many forms of learning, including contextual fear, spatial memory, instrumental learning and Pavlovian reward memory (6). However, learning-induced transcriptional changes within the NAc have not been examined (7, 8). Given that de novo transcription is required for memory formation (9) and that the NAc is a hub for reward, memory and drug seeking, mechanisms contributing to memory-induced transcriptional changes in the NAc may provide insight into approaches aimed at disrupting METH-associated memories.…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine-Associated Memory Is Regulated by a Writer and an Eraser of Permissive Histone Methylation

Aguilar‐Valles

Vaissière

Griggs

et al. 2014

Biological Psychiatry

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Background Memories associated with drugs of abuse, such as methamphetamine (METH), increase relapse vulnerability to substance use disorder by triggering craving. The nucleus accumbens (NAc) is essential to these drug-associated memories, but underlying mechanisms are poorly understood. Posttranslational chromatin modifications, such as histone methylation, modulate gene transcription, thus we investigated the role of the associated epigenetic modifiers in METH-associated memory. Methods Conditioned place preference was used to assess the epigenetic landscape in the NAc supporting METH-associated memory (n=79). The impact of histone methylation (H3K4me2/3) on the formation and expression of METH-associated memory was determined by focal, intra NAc knockdown (KD) of a writer, the methyltransferase MLL1 (n=26), and an eraser, the histone demethylase KDM5C (n=38), of H3K4me2/3. Results A survey of chromatin modifications in the NAc of animals forming a METH-associated memory revealed the global induction of several modifications associated with active transcription. This correlated with a pattern of gene activation, as revealed by microarray analysis, including upregulation of Oxtr and Fos, whose promoters also had increased H3K4me3. KD of Mll1 reduced H3K4me3, Fos and Oxtr levels and disrupted METH-associated memory. KD of Kdm5c resulted in hypermethylation of H3K4 and prevented the expression of METH-associated memory. Conclusions The development and expression of METH-associated memory are supported by regulation of H3K4me2/3 levels by MLL1 and KDM5C, respectively, in the NAc. These data indicate that permissive histone methylation, and the associated epigenetic writers and erasers, represent potential targets for the treatment of substance abuse relapse, a psychiatric condition perpetuated by unwanted associative memories.

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CM156, a sigma receptor ligand, reverses cocaine-induced place conditioning and transcriptional responses in the brain

Cited by 19 publications

References 39 publications

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

Sigma receptor antagonists attenuate acute methamphetamine-induced hyperthermia by a mechanism independent of IL-1β mRNA expression in the hypothalamus

A role for sigma receptors in stimulant self-administration and addiction

Methamphetamine-Associated Memory Is Regulated by a Writer and an Eraser of Permissive Histone Methylation

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