An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice

Hummel, Michele; Schroeder, Joseph A.; Liu‐Chen, Lee‐Yuan; Cowan, Alan; Unterwald, Ellen M.

doi:10.1016/j.neuroscience.2006.06.013

Cited by 22 publications

(20 citation statements)

References 90 publications

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“…Recently, we have demonstrated that mice receiving i.c.v. injections of an antisense oligonucleotide directed against the mu opioid receptor failed to sensitize to cocaine (Hummel et al 2006). In contrast to these findings, Lesscher et al 2005 pretreated mice with CTOP, another selective mu receptor antagonist peptide, by peripheral (i.p.)…”

Section: Discussionmentioning

confidence: 76%

“…Adding to the importance specifically of the mu opioid receptor in cocaine reward, we have recently shown that mice receiving an antisense oligonucleotide directed at the mu opioid receptor do not exhibit conditioned place preference to cocaine (Hummel et al 2006). We (unpublished observation) and others (Hall et al 2004) have found that the rewarding properties of cocaine are reduced in mu opioid receptor knockout mice.…”

Section: Discussionmentioning

confidence: 78%

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A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat

et al. 2007

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 78%

A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat

et al. 2007

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“…In fact, we have reported that rats maintained on high-dose methadone maintenance show no cocaine-place preference and no cocaine-induced up-regulation of mu-opioid receptor mRNA in the nucleus accumbens core (Leri et al, 2006). This is notable because the effect of cocaine exposure on mu-opioid receptor density and function in mesocorticolimbic areas (Azaryan et al, 1996;Unterwald et al, 1992;Unterwald, 2001;Yuferov et al, 1999) has been associated to the intensity of cocaine cravings in humans (Gorelick et al, 2005;Zubieta et al, 1996), and to a variety of behavioral, electrophysiological and neurochemical responses to cocaine in animals (Mathon et al, 2005a(Mathon et al, , b, 2006Tang et al, 2005;Hummel et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

Leri

Sorge

Cummins

et al. 2007

Neuropsychopharmacol

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It has been demonstrated that high-dose methadone maintenance is efficacious in reducing cocaine abuse in opioid-dependent individuals, but it is not clear whether this is caused by an action of methadone on the direct reinforcing properties of cocaine or on cocaine seeking. Also, it is not clear whether high-dose methadone maintenance may induce behavioral side effects, which could limit its clinical use. Here, we report that high-dose methadone maintenance (20-40 mg/kg/day) does not reduce, and even enhances cocaine (10-30 mg/kg, i.p.)-induced elevation in dopamine concentration in the ventral striatum measured by in vivo microdialysis. In parallel, however, rats maintained on high-dose methadone (30 mg/kg/day) seek and consume significantly less cocaine than controls when tested for intravenous cocaine (0.5 mg/kg/infusion) self-administration on a progressive ratio schedule of reinforcement. This reduction in cocaine self-administration does not result from impaired sensory-motor functioning as rats maintained on high-dose methadone show normal locomotor activity. Furthermore, the reduction in responding for cocaine does not seem to result from general behavioral deficits as male rats maintained on high methadone doses respond normally to palatable food and thermal pain, although their sexual responses to receptive females are greatly suppressed. Taken together, these results from studies in rats support the usefulness of larger doses of methadone to reduce severe cocaine abuse in opioid-dependent individuals and possibly in the management of pure-cocaine addiction.

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“…A randomized unbiased conditioned place preference procedure was used as described by us (Hummel et al 2006) with some minor modifications. Conditioned place preference chambers were rectangular in shape (45 × 20 × 20 cm) and consisted of two compartments, separated by a removable door.…”

Section: Methodsmentioning

confidence: 99%

Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition

et al. 2014

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Rational Memories return to a labile state following their retrieval and must undergo a process of reconsolidation to be maintained. Thus, disruption of cocaine reward memories by interference with reconsolidation may be therapeutically beneficial in the treatment of cocaine addiction. Objective The objectives were to elucidate the signaling pathway involved in reconsolidation of cocaine reward memory and to test whether targeting this pathway could disrupt cocaine-associated contextual memory. Methods Using a mouse model of conditioned place preference, regulation of the activity of glycogen synthase kinase-3 (GSK3), mammalian target of Rapamycin complex 1 (mTORC1), P70S6K, β-catenin, and the upstream signaling molecule Akt, was studied in cortico-limbic-striatal circuitry after re-exposure to an environment previously paired with cocaine. Result Levels of phosporylated Akt-Thr308, GSK3α-Ser21, GSK3β-Ser9, mTORC1, and P70S6K were reduced in the nucleus accumbens and hippocampus 10 min after the reactivation of cocaine cue memories. Levels of pAkt and pGSK3 were also reduced in the prefrontal cortex. Since reduced phosphorylation of GSK3 indicates heightened enzyme activity, the effect of a selective GSK3 inhibitor, SB216763, on reconsolidation was tested. Administration of SB216763 immediately after exposure to an environment previously paired with cocaine abrogated a previously established place preference, suggesting that GSK3 inhibition interfered with reconsolidation of cocaine-associated reward memories. Conclusions These findings suggest that the Akt/GSK3/ mTORC1 signaling pathway in the nucleus accumbens, hippocampus, and/or prefrontal cortex is critically involved in the reconsolidation of cocaine contextual reward memory. Inhibition of GSK3 activity during memory retrieval can erase an established cocaine place preference.

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An antisense oligodeoxynucleotide to the mu opioid receptor attenuates cocaine-induced behavioral sensitization and reward in mice

Cited by 22 publications

References 90 publications

A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat

A role for mu opioid receptors in cocaine-induced activity, sensitization, and reward in the rat

High-Dose Methadone Maintenance in Rats: Effects on Cocaine Self-Administration and Behavioral Side Effects

Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition

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