A conditioned place preference for heroin is signaled by increased dopamine and direct pathway activity and decreased indirect pathway activity in the nucleus accumbens

Tj, O'Neal; Bernstein, Mollie; Dj, MacDougall; Sm, Ferguson

doi:10.1101/2021.07.14.452340

Cited by 7 publications

(14 citation statements)

References 49 publications

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“…10,13,44,45 Here, Hsp70 expression was reduced only in the NAc shell and unchanged in the mPFC, VTA and NAc core, suggesting a specific role for the NAc shell in incentive motivation and drug-paired memories induced by morphine. 7,46 In this study, icv PES and KNK437 were both demonstrated to inhibit the development and expression of morphine CPP in rats. MB suppressed CPP during development but not expression.…”

Section: Discussionmentioning

confidence: 60%

“…The NAc shell is primarily involved in cue‐induced reinstatement and conditioned stimulus effects, whereas the NAc core primarily mediates responses in drug‐paired conditioned reinforcement 10,13,44,45 . Here, Hsp70 expression was reduced only in the NAc shell and unchanged in the mPFC, VTA and NAc core, suggesting a specific role for the NAc shell in incentive motivation and drug‐paired memories induced by morphine 7,46 …”

Section: Discussionmentioning

confidence: 81%

“…CPP is a classic paradigm that measures the association between the putative reinforcing properties of a drug with the previously neutral cues and/or contextual features present in the environment in which the drug is experienced and has long been used to evaluate the rewarding effects of drugs of abuse 6 . The mesocorticolimbic, or rewarding system, consisting of dopaminergic neurons originating in the ventral tegmental area (VTA) and projecting to the NAc and medial prefrontal cortex (mPFC), are critical for CPP to drugs of abuse, including morphine 3,7–9 . For example, doses of morphine that produce significant morphine CPP have been shown to result in increased dopamine release in the NAc, as measured using microdialysis 6 .…”

Section: Introductionmentioning

confidence: 99%

“…6 The mesocorticolimbic, or rewarding system, consisting of dopaminergic neurons originating in the ventral tegmental area (VTA) and projecting to the NAc and medial prefrontal cortex (mPFC), are critical for CPP to drugs of abuse, including morphine. 3,[7][8][9] For example, doses of morphine that produce significant morphine CPP have been shown to result in increased dopamine release in the NAc, as measured using microdialysis. 6 Furthermore, the lesions of the NAc, and dopaminergic agonists and antagonists administered peripherally or into the NAc prior to morphine conditioning, have been shown to alter morphine CPP.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 Heat shock protein is a molecular chaperone that aids in protein folding and prevents protein aggregation in cells. 12,13 Hsp70 is a critical molecule abundantly expressed in the eukaryotic cytosol, 7 and the dysfunction of Hsp70 has been found to be associated with cancer, apoptosis, neurodegenerative and infectious diseases. 12,13 In addition, Hsp70 has been identified as a potential biomarker for addiction, 14 yet few studies to date have investigated the role of Hsp70 in the development and expression of CPP to drugs of abuse such as morphine.…”

Section: Introductionmentioning

confidence: 99%

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Molecular chaperone heat shock protein 70 inhibitors suppress conditioned place preference induced by morphine exposure in male rats

Wei

Gong

et al. 2022

Addiction Biology

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Previous studies have indicated a role for molecular chaperone heat shock protein 70 (Hsp70) in the development of behavioural sensitization to morphine in rodents, suggesting that Hsp70 expression following morphine exposure is involved in molecular changes that may underlie addiction vulnerability. The current study was carried out to investigate the role of Hsp70 in the positive reinforcing properties of morphine using conditioned place preference (CPP) in male rats. An unbiased CPP procedure of three phases (pre-conditioning: d1-d3; conditioning: d4-d6; and testing: d7) was used. During the conditioning phase, morphine injections (5 mg/kg, subcutaneously) were administered to induce significant place preference. To explore the effect of Hsp70 on the development and expression of morphine CPP, Hsp70 inhibitors (PES, KNK437 and methylene blue) were administered into the lateral ventricle prior to either morphine conditioning sessions or a morphine challenge on the test day. Furthermore, Hsp70 expression within the mesocorticolimbic system was measured after the treatment with KNK437, a transcriptional inhibitor. We found that PES and KNK437, respectively, injected intracerebroventricularly dose-dependently attenuated both the development and expression of morphine CPP. Methylene blue treatment demonstrated an attenuation of the development, but had no effect on the expression of morphine CPP. Following KNK437 treatment, Hsp70 expression was significantly inhibited in the shell of nucleus accumbens (NAc) during both the development and expression of morphine CPP. The findings suggest that Hsp70 in the NAc shell plays an important role in the reinforcing effects of morphine and may be involved in the development of morphine dependence.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Molecular chaperone heat shock protein 70 inhibitors suppress conditioned place preference induced by morphine exposure in male rats

Wei

Gong

et al. 2022

Addiction Biology

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Characterization and mu opioid receptor sensitivity of neuropeptide Y interneurons in the nucleus accumbens

Retzlaff

Rothwell

2022

Preprint

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Inhibitory interneurons represent less than 5% of neurons within the nucleus accumbens, but are critical for proper microcircuit function within this brain region. In the dorsal striatum, neuropeptide Y is expressed by two interneuron subtypes (low-threshold spiking interneurons and neurogliaform interneurons) that exhibit mu opioid receptor sensitivity in other brain regions. However, few studies have assessed the molecular and physiological properties of neuropeptide Y interneurons within the nucleus accumbens. We used a transgenic reporter mouse to identify and characterize neuropeptide Y interneurons in acute nucleus accumbens brain slices. Nearly all cells exhibited electrophysiological properties of low-threshold spiking interneurons, with almost no neurogliaform interneurons observed among neuropeptide Y interneurons. We corroborated this pattern using fluorescent in situ hybridization, and also identified a high level of mu opioid receptor expression by low-threshold spiking interneurons, which led us to examine the functional consequences of mu opioid receptor activation in these cells using electrophysiology. Mu opioid receptor activation caused a reduction in the rate of spontaneous action potentials in low-threshold spiking interneurons, as well as a decrease in optogenetically-evoked GABA release onto medium spiny neurons. The latter effect was more robust in female versus male mice, and when the postsynaptic medium spiny neuron expressed the Drd1 dopamine receptor. This work is the first to examine the physiological properties of neuropeptide Y interneurons in the nucleus accumbens, and show they may be an important target for mu opioid receptor modulation by endogenous and exogenous opioids.

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Pyfiber: an open source python library that facilitates the merge of operant behavior and fiber photometry- focus on intravenous self-administration

Conlisk

Ceau

Fiancette

et al. 2022

Preprint

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Background- Advances in in vivo fluorescent imaging have exploded with the recent developments of genetically encoded calcium indicators (GECIs) and fluorescent biosensors. Their use with a bulk imaging technique such as fiber photometry (FP) can be highly beneficial in identifying neuronal signatures in behavioral neuroscience experiments. Popularity of FP has grown rapidly. Initially applied to classical conditioning, its integration into operant behavior paradigms is progressing. However, in operant behavior, protocols can be complex including numerous scheduled events, while behavioral responses can occur in diverse and non-predictable manners. To optimize data processing and analysis, there is a need for a flexible tool to extract and relate behavioral and fiber photometry data occurring over operant sessions. New Method- Applied to cocaine intravenous self-administration (using ImetronicR polymodal apparati) and FP recordings in the prelimbic cortex (using Doric Lenses photometry system) in the rat, we established Pyfiber, an outline and open source data analysis python library that facilitates the merge of fiber photometry (using Doric Lenses) with operant behavior (using ImetronicR). It allows relating activity changes within a neuronal population to the various behavioral responses and events occurring during operant behavior. Results- We show some of the possibilities and benefits of the analytical tool Pyfiber, which helps to: 1. Extract the different types of events that occur in an operant session, 2. Extract and process the fiber photometry signals, 3. Select events of interest and align them to the corresponding fiber photometry signals, 4. Apply the most appropriate type of FP signal normalization and signal analysis according to the studied type of event or behavioral response, 5. Run data extraction and analysis on multiple individuals and sessions at the same time, 6. Collect results in an easily readable format for statistical analysis. From our data and through the use of Pyfiber, we show that we can successfully record and easily analyze calcium transients surrounding events occurring during a cocaine self-administration paradigm in the rat. Comparison with Existing Method(s)- While other analytical tools can be used for streamlined fiber photometry analysis, they are either too rigid and specific or too flexible, requiring extensive coding to properly fit the data sets. Additionally, current tools do not permit easy exploration of multiple types of events in parallel- something that is possible with Pyfiber. Conclusions- This work established an open source resource that facilitates the pairing of fiber photometry recordings (using Doric Lenses photometry system) with operant behavior (using ImetronicR polymodal apparati), setting a solid foundation in analyzing the relationship between different dimensions of operant behavior with fluorescent signals from brain regions of interest.

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A conditioned place preference for heroin is signaled by increased dopamine and direct pathway activity and decreased indirect pathway activity in the nucleus accumbens

Cited by 7 publications

References 49 publications

Molecular chaperone heat shock protein 70 inhibitors suppress conditioned place preference induced by morphine exposure in male rats

Molecular chaperone heat shock protein 70 inhibitors suppress conditioned place preference induced by morphine exposure in male rats

Characterization and mu opioid receptor sensitivity of neuropeptide Y interneurons in the nucleus accumbens

Pyfiber: an open source python library that facilitates the merge of operant behavior and fiber photometry- focus on intravenous self-administration

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