New operant model of reinstatement of food-seeking behavior in mice

Martín‐García, Elena; Burokas, Aurelijus; Kostrzewa, Elzbieta; Gieryk, Agnieszka; Korostyński, Michał; Ziółkowska, Barbara; Przewłocka, Barbara; Przewłocki, Ryszard; Maldonado, Rafaël

doi:10.1007/s00213-010-2110-6

Cited by 34 publications

(27 citation statements)

References 74 publications

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“…We have used a reliable operant model of reinstatement validated in our laboratory (Martin-Garcia et al, 2011;Soria et al, 2008) to demonstrate that the constitutive deletion of MOR, DOR, PENK, and PDYN differentially modifies the acquisition and reinstatement of cocaineseeking behavior, but has no significant consequences in a similar operant training for palatable food. Indeed, a similar performance in operant responding maintained by food was obtained in all knockout mice and wild-type littermates under our experimental conditions, which ruled out a potential learning impairment for operant training in these four lines of knockout mice.…”

Section: Discussionmentioning

confidence: 99%

“…under fixed ratio 1 (FR1) (5 consecutive days) and FR3 (7 consecutive days). The criteria for acquisition of operant responding were achieved when mice maintained a stable responding with less than 20% deviation from the mean of the total number of infusions earned in three consecutive sessions, with at least 75% responding on the reinforced nose-poke, and a minimum of 10 reinforcements per session (Martin-Garcia et al, 2011;Soria et al, 2008). After the 12 FR sessions, animals were tested in a progressive ratio (PR) schedule where the response requirement to earn infusions escalated according to the following series: 1-2-3- 5-12-18-27-40-60-90-135-200-300-450-675-1000.…”

Section: Experimental Designmentioning

confidence: 99%

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Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

Gutiérrez‐Cuesta

Burokas

Mancino

et al. 2014

Neuropsychopharmacol

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The repeated cycles of cessation of consumption and relapse remain the major clinical concern in treating drug addiction. The endogenous opioid system is a crucial component of the reward circuit that participates in the adaptive changes leading to relapse in the addictive processes. We have used genetically modified mice to evaluate the involvement of m-opioid receptor (MOR) and d-opioid receptor (DOR) and their main endogenous ligands, the enkephalins derived from proenkephalin (PENK) and prodynorphin (PDYN), in the reinstatement of cocaine-seeking behavior. Constitutive knockout mice of MOR, DOR, PENK, and PDYN, and their wild-type littermates were trained to self-administer cocaine or to seek for palatable food, followed by a period of extinction and finally tested on a cue-induced reinstatement of seeking behavior. The four lines of knockout mice acquired operant cocaine self-administration behavior, although DOR and PENK knockout mice showed less motivation for cocaine than wild-type littermates. Moreover, cue-induced relapse was significantly decreased in MOR and DOR knockout mice. In contrast, PDYN knockout mice showed a slower extinction and increased relapse than wild-type littermates. C-Fos expression analysis revealed differential activation in brain areas related with memory and reward in these knockout mice. No differences were found in any of the four genotypes in operant responding to obtain palatable food, indicating that the changes revealed in knockout mice were not due to unspecific deficit in operant performance. Our results indicate that MOR, DOR, and PDYN have a differential role in cue-induced reinstatement of cocaine-seeking behavior.

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

Gutiérrez‐Cuesta

Burokas

Mancino

et al. 2014

Neuropsychopharmacol

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“…on an FR1 schedule over a time period of seven days. The criteria for acquisition of operant responding were achieved when mice maintained a stable responding with less than 25% deviation from the mean of the total number of infusions earned in three consecutive sessions, with at least 65% responding on the reinforced nose-poke, and a minimum of four reinforcements per session (Martin-Garcia et al, 2011; Soria et al, 2008). From days 8 to 15 (eight sessions), mice received their appropriate drug injection 60 min before each FR1 training session.…”

Section: Methodsmentioning

confidence: 99%

The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice

et al. 2017

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Although opioids are highly efficacious analgesics, their abuse potential and other untoward side effects diminish their therapeutic utility. The addition of non-opioid analgesics offers a promising strategy to reduce required antinociceptive opioid doses that concomitantly reduce opioid-related side effects. Inhibitors of the primary endocannabinoid catabolic enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) show opioid-sparing effects in preclinical models of pain. As simultaneous inhibition of these enzymes elicits enhanced antinociceptive effects compared with single enzyme inhibition, the present study tested whether the dual FAAH-MAGL inhibitor SA-57 [4-[2-(4-chlorophenyl)ethyl]-1-piperidinecarboxylic acid 2-(methylamino)-2-oxoethyl ester] produces morphine-sparing antinociceptive effects, without major side effects associated with either drug class. SA-57 dose-dependently reversed mechanical allodynia in the constriction injury (CCI) of the sciatic nerve model of neuropathic pain and carrageenan inflammatory pain model. As previously reported, SA-57 was considerably more potent in elevating anandamide (AEA) than 2-arachidonyl glycerol (2-AG) in brain. Its anti-allodynic effects required cannabinoid (CB)1 and CB2 receptors; however, only CB2 receptors were necessary for the anti-edematous effects in the carrageenan assay. Although high doses of SA-57 alone were required to produce antinociception, low doses of this compound, which elevated AEA and did not affect 2-AG brain levels, augmented the antinociceptive effects of morphine, but lacked cannabimimetic side effects. Because of the high abuse liability of opioids and implication of the endocannabinoid system in the reinforcing effects of opioids, the final experiment tested whether SA-57 would alter heroin seeking behavior. Strikingly, SA-57 reduced heroin-reinforced nose poke behavior and the progressive ratio break point for heroin. In conclusion, the results of the present study suggest that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse.

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“…Some limitations to this approach do exist, such as unintended escaping of LED light acting as a behavioral cue during stimulation. 54,55 3 Devices…”

Section: Fiber Couplingmentioning

confidence: 99%

Evolution of optogenetic microdevices

et al. 2015

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Abstract. Implementation of optogenetic techniques is a recent addition to the neuroscientists' preclinical research arsenal, helping to expose the intricate connectivity of the brain and allowing for on-demand direct modulation of specific neural pathways. Developing an optogenetic system requires thorough investigation of the optogenetic technique and of previously fabricated devices, which this review accommodates. Many experiments utilize bench-top systems that are bulky, expensive, and necessitate tethering to the animal. However, these bench-top systems can make use of power-demanding technologies, such as concurrent electrical recording. Newer portable microdevices and implantable systems carried by freely moving animals are being fabricated that take advantage of wireless energy harvesting to power a system and allow for natural movements that are vital for behavioral testing and analysis. An investigation of the evolution of tethered, portable, and implantable optogenetic microdevices is presented, and an analysis of benefits and detriments of each system, including optical power output, device dimensions, electrode width, and weight is given. Opsins, light sources, and optical fiber coupling are also discussed to optimize device parameters and maximize efficiency from the light source to the fiber, respectively. These attributes are important considerations when designing and developing improved optogenetic microdevices.

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New operant model of reinstatement of food-seeking behavior in mice

Abstract: This study provides a new operant model in mice for the evaluation of food-taking behavior and reveals specific changes in the dopamine and opioid system associated to the behavioral responses directed to obtain a natural reward.

Cited by 34 publications

References 74 publications

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

Effects of Genetic Deletion of Endogenous Opioid System Components on the Reinstatement of Cocaine-Seeking Behavior in Mice

The endocannabinoid hydrolysis inhibitor SA-57: Intrinsic antinociceptive effects, augmented morphine-induced antinociception, and attenuated heroin seeking behavior in mice

Evolution of optogenetic microdevices

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