Cocaine Self-Administration Reduces Excitatory Responses in the Mouse Nucleus Accumbens Shell

Schramm-Sapyta, Nicole L.; Olsen, Christopher M.; Winder, Danny G.

doi:10.1038/sj.npp.1300918

Cited by 53 publications

(47 citation statements)

References 45 publications

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“…For example, prolonged cocaine treatment (but not following a single injection) decreases the AMPA/NMDA receptor ratio in the NAc shell (Thomas et al, 2001). In addition, cocaine self-administration produces a postsynaptic decrease in the AMPA receptormediated fEPSP (Schramm-Sapyta et al, 2006). Finally, many studies have demonstrated changes in glutamate receptor subunit levels in the NAc following exposure to either cocaine or amphetamine (Lu et al, 1997 Acute amphetamine alters j-opioid function Y Xia et al Churchill et al, 1999;.…”

Section: Discussionmentioning

confidence: 99%

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Xia

Whistler

et al. 2007

Neuropsychopharmacol

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In the present study, we investigated the effects of psychostimulant exposure on k-opioid peptide (KOP) receptor signaling in the rat mesolimbic system. A single subcutaneous (s.c.) injection of amphetamine (2.5 mg/kg) reduced the KOP receptor-mediated inhibition of glutamate release in the nucleus accumbens shell, as a consequence of KOP receptor desensitization. This effect was blocked by dopamine (DA) receptor antagonists or the nonselective opioid antagonist, naltrexone (1 mg/kg, s.c.), and mimicked by the KOP receptor agonists U69593 (0.32 mg/kg, s.c.) and dynorphin (1 mM), indicating that an amphetamine-induced release of dynorphin is producing a long-lasting desensitization of the KOP receptor. Despite the fact that amphetamine also increases dynorphin release in the ventral tegmental area (VTA), KOP receptor function in this region was not affected by amphetamine; there was no difference in the KOP receptor-mediated change in firing rate or resting membrane potential measured in VTA neurons from saline-or amphetaminetreated animals. This study demonstrates that amphetamine can produce regionally selective adaptations in KOP receptor signaling, which may, in turn, alter the effects of subsequent drug exposure.

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Section: Discussionmentioning

confidence: 99%

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Xia

Whistler

et al. 2007

Neuropsychopharmacol

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“…One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher [10][11][12][13][14][15] . Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors.…”

Section: Introductionmentioning

confidence: 86%

Operant Sensation Seeking in the Mouse

Olsen

Winder

2010

JoVE

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Operant methods are powerful behavioral tools for the study of motivated behavior. These 'self-administration' methods have been used extensively in drug addiction research due to their high construct validity. Operant studies provide researchers a tool for preclinical investigation of several aspects of the addiction process. For example, mechanisms of acute reinforcement (both drug and non-drug) can be tested using pharmacological or genetic tools to determine the ability of a molecular target to influence self-administration behavior 1-6 . Additionally, drug or food seeking behaviors can be studied in the absence of the primary reinforcer, and the ability of pharmacological compounds to disrupt this process is a preclinical model for discovery of molecular targets and compounds that may be useful for the treatment of addiction 3,7-9 . One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher [10][11][12][13][14][15] . Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors. For example, measurement of the reinforcing and neurological effects of psychostimulants can be confounded by their psychomotor effects. Operant methods using food reinforcement can avoid these pitfalls, although their utility in studying drug addiction is limited by the fact that some manipulations that alter drug self-administration have a minimal impact on food self-administration. For example, mesolimbic dopamine lesion or knockout of the D1 dopamine receptor reduce cocaine self-administration without having a significant impact on food self-administration 12,16 . Sensory stimuli have been described for their ability to support operant responding as primary reinforcers (i.e. not conditioned reinforcers) [17][18][19][20][21][22] . Auditory and visual stimuli are self-administered by several species 18,21,23 , although surprisingly little is known about the neural mechanisms underlying this reinforcement. The operant sensation seeking (OSS) model is a robust model for obtaining sensory self-administration in the mouse, allowing the study of neural mechanisms important in sensory reinforcement 24 . An additional advantage of OSS is the ability to screen mutant mice for differences in operant behavior that may be relevant to addiction. We have reported that dopamine D1 receptor knockout mice, previously shown to be deficient in psychostimulant self-administration, also fail to acquire OSS 24 . This is a unique finding in that these mice are capable of learning an operant task when food is used as a reinforcer. While operant studies using food reinforcement can be useful in the study of general motivated behavior and the mechanisms underlying food reinforcement, as mentioned above, these studies are limited in their application to studying molecular mechanisms of drug addiction...

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“…The maintenance or lasting expression of behavioral sensitization to cocaine is, however, dependent upon the ventral striatum, and upon NAc glutamate transmission in particular (Bell et al, 2000;Pierce et al, 1996;Vanderschuren and Kalivas, 2000). Plasticity of NAc glutamatergic synapses has been associated with both cocaine sensitization (Brebner et al, 2005;Goto and Grace, 2005;Thomas et al, 2001;Yao et al, 2004) and cocaine-seeking behaviors (Martin et al, 2006;Schramm-Sapyta et al, 2006). CB 1 receptors are functionally expressed on glutamatergic axon terminals onto NAc output neurons (Robbe et al, 2001), and cocaine has been reported to alter the plasticity of these synapses (Fourgeaud et al, 2004).…”

Section: Possible Sites and Mechanism Of Actionmentioning

confidence: 99%

“…Behavioral sensitization to cocaine or amphetamine has been correlated to the expression and occlusion of longterm depression (LTD) of excitatory synaptic transmission in the NAc (Thomas et al, 2001;Brebner et al, 2005). It was also recently reported that excitatory neurotransmission was reduced (Schramm-Sapyta et al, 2006) and LTD was abolished (Martin et al, 2006) in the NAc after animals were trained to self-administer cocaine, but not following noncontingent cocaine administration.…”

Section: Introductionmentioning

confidence: 99%

Context-Specific Reversal of Cocaine Sensitization by the CB1 Cannabinoid Receptor Antagonist Rimonabant

Gerdeman

Schechter

French

2007

Neuropsychopharmacol

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The CB 1 cannabinoid receptor is implicated in the rewarding properties of many drugs of abuse, including cocaine. While CB 1 receptor involvement in the acute rewarding properties of cocaine is controversial, CB 1 antagonists such as SR141716 (rimonabant) have clearly been found to prevent cue-and cocaine-elicited reinstatement of cocaine self-administration in rodents. Here we demonstrate the novel involvement of CB 1 receptors in the maintenance of behavioral sensitization to cocaine in C57BL/6 mice. Consistent with previous reports, the induction of locomotor sensitization following repeated daily cocaine was not prevented by systemic pretreatment of either rimonabant, D 9 -tetrahydrocannabinol (THC), or a 1:1 mixture of THC and cannabidiol (CBD). In contrast, established cocaine sensitization was markedly disrupted following subchronic treatment with rimonabant alone. This effect was notably context-dependent, in that rimonabant did not diminish established cocaine sensitization if delivered in the home cage, but only if the rimonabant-injected mice were exposed to activity chambers previously paired with cocaine. These findings are consistent with CB 1 receptor involvement in conditioned cocaine-seeking behaviors, and further suggest that endocannabinoid (eCB)-mediated synaptic plasticity may act specifically within drug-paired environments to maintain cocaine-directed behavioral responses.

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Cocaine Self-Administration Reduces Excitatory Responses in the Mouse Nucleus Accumbens Shell

Cited by 53 publications

References 45 publications

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Acute Amphetamine Exposure Selectively Desensitizes κ-Opioid Receptors in the Nucleus Accumbens

Operant Sensation Seeking in the Mouse

Context-Specific Reversal of Cocaine Sensitization by the CB1 Cannabinoid Receptor Antagonist Rimonabant

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