Subjective perception of cocaine reward in mice assessed by a single exposure place preference (sePP) paradigm

Runegaard, Annika H.; Jensen, Kathrine L.; Dencker, Ditte; Wörtwein, Gitta; Gether, Ulrik

doi:10.1016/j.jneumeth.2017.07.010

Cited by 7 publications

(21 citation statements)

References 28 publications

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“…(D) Place preference test in male mice the day after single exposures to each compartment. Mice that were exposed once to cocaine (10 mg/kg) in the grey (nonpreferred compartment (Runegaard et al ., )) spent more time in this compartment as compared to mice that were exposed to saline in both compartments t (14)=2.297, P = 0.0376, unpaired t test, N : 8 saline, 8 cocaine).…”

Section: Resultsmentioning

confidence: 97%

“…1A). We have previously shown that mice exhibit a strong bias towards the striped compartment, and that a single exposure of cocaine administered intraperitoneally immediately before the mouse is placed in the grey compartment is sufficient to change the preference towards this compartment when exposure sessions were conducted over 2 days (Runegaard et al, 2017). Here, we have shortened the protocol with both exposure sessions conducted on day 1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Single-exposure place preference-experiments were performed in a three-compartment elongated rectangular apparatus (67.5 9 24 cm, 40 cm high) without lid, for an unforced-choice procedure with a predictable, biased design. The apparatus has a neutral zone (11.5 9 24 cm) in the middle, separating two elongated compartments (28 9 24 cm) with different floor textures and wall patterns described in further detail in (Runegaard et al, 2017). During the exposure sessions, the compartments were closed off by two offwhite Plexiglas â partitions (24 9 40 cm) inserted between the neutral zone and the two outer compartments.…”

Section: Conditioning Apparatusmentioning

confidence: 99%

“…The sePP protocol was conducted over 2 days, with both exposure sessions on the first day and preference testing on the following morning. On both days, mice were moved from the housing facility to the experimental room and allowed to acclimatize for at least 1 h. Drug (cocaine/amphetamine) was always paired with the compartment having a grey wall and a punched pattern on the floor, which was previously shown to be the least preferred compartment (Runegaard et al, 2017). All mice from a cage were tested at the same time, but not necessarily given the same treatment.…”

Section: Place Preference Protocolmentioning

confidence: 99%

“…We have recently established an alternative to the classical CPP paradigm, a single-exposure place preference (sePP) procedure allowing assessment of initial reward-perception of cocaine with a protocol lasting 3 days (Runegaard et al, 2017). The sePP is an easy-to-implement and timesaving protocol complementing the classic paradigms of addiction research to link the acute effects of addictive drugs with subsequent effects and behaviours like extinction and reinstatement.…”

Section: Introductionmentioning

confidence: 99%

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Initial rewarding effects of cocaine and amphetamine assessed in a day using the single‐exposure place preference protocol

Runegaard

Jensen

Wörtwein

et al. 2018

Eur J of Neuroscience

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In rodents, only a single dose of cocaine or amphetamine is required to cause a marked increase in extracellular dopamine, induce hyperlocomotion and cause persistent plasticity changes within dopaminergic neurons of the ventral tegmental area (VTA). The initial drug experience is suggested to predict vulnerability of developing addiction, but only few studies have assessed the perception of reward accompanying this initial exposure. We recently presented an approach to assess the initial rewarding effects of cocaine in mice with a single-exposure place preference (sePP) protocol, avoiding repeated drug injections. Here, we demonstrate a condensed version of the sePP, allowing assessment of initial subjective reward-perception within a day. By using this protocol, we demonstrate that a single exposure to both cocaine and amphetamine is sufficient to induce place preference. Furthermore, we use chemogenetics ( Designer Receptors Exclusively Activated by Designer Drugs [DREADD]) to show that both inhibitory and stimulatory modulation of VTA DA signalling disrupts cocaine-induced place preference in the condensed sePP. Our findings support the presence of initial reward-perception of both cocaine and amphetamine, and the formation of drug-context association. In addition, our data support that VTA DA signalling prior to drug exposure affects either reward-perception or the time during which associations are formed, thereby preventing induction of cocaine-induced place preference in the sePP. The easy and timesaving sePP protocol should form a critical basis for further deciphering the complex mechanisms underlying the progression from the initial drug experience to escalating drug intake and addiction.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Conditioning Apparatusmentioning

confidence: 99%

Section: Place Preference Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Initial rewarding effects of cocaine and amphetamine assessed in a day using the single‐exposure place preference protocol

Runegaard

Jensen

Wörtwein

et al. 2018

Eur J of Neuroscience

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mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Jensen,

Chistensen,

Goddard

et al. 2023

Preprint

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Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting one in five adults. Current treatment is compromised by dose-limiting side effects including high abuse liability, loss of ability to function socially and professionally, fatigue, drowsiness, and apathy. PICK1 has emerged as a promising target for the treatment of chronic pain conditions. Here, we develop and characterize a cell-permeable fatty acid conjugated bivalent peptide inhibitor of PICK1 and assess its effects on acute and chronic pain. The myristoylated myr-NPEG4-(HWLKV)2, (mPD5), self-assembles into core-shell micelles that provide favourable pharmacodynamic properties and relieves ongoing and evoked mechanical hypersensitivity, thermal hypersensitivity as well as anxio-depressive symptoms in mouse models of neuropathic and inflammatory pain following subcutaneous administration. No overt no side effects were associated with mPD5 administration, and it has no effect on acute nociception. Finally, neuropathic pain is relieved far into the chronic phase (18 weeks post SNI surgery) and while the effect of a single injection ceases after a few hours, repeated administration provides pain relief lasting up to 20 hours after the last injection.

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Distinct ventral tegmental area neuronal ensembles are indispensable for reward-driven approach and stress-driven avoidance behaviors

Koutlas,

Patrikiou,

van der Starre

et al. 2024

Preprint

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Assigning valence to stimuli for adaptive behavior is an essential function, involving the ventral tegmental area (VTA). VTA cell types are often defined through neurotransmitters (NT). However, valence function in VTA does not parse along NT-boundaries as, within each NT-class, certain neurons are excited by reward and others by stressors. Here we identify the co-activated mouse VTA neuronal ensembles for reward and stress, and determine their role in adaptive behaviors. We show that stimuli of opposite valence (opioid vs acute social stress) recruit two segregated intermingled small VTA neuronal ensembles. These two ensembles continue to be preferentially engaged by congruent valence stimuli. Stimulation of VTA stress- or reward ensembles is aversive/reinforcing, respectively. Strikingly, external valence stimuli fully require activity of these small discrete VTA ensembles for conferring approach/avoidance outcomes. Overall, our study identifies distinct small VTA ensembles for positive and negative valence coding and shows their indispensability for adaptive behavior.

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Subjective perception of cocaine reward in mice assessed by a single exposure place preference (sePP) paradigm

Cited by 7 publications

References 28 publications

Initial rewarding effects of cocaine and amphetamine assessed in a day using the single‐exposure place preference protocol

Initial rewarding effects of cocaine and amphetamine assessed in a day using the single‐exposure place preference protocol

mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain

Distinct ventral tegmental area neuronal ensembles are indispensable for reward-driven approach and stress-driven avoidance behaviors

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