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Alcohol drinking under intermittent access in group-housed C57BL/6J mice

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Smutek M., Rodriguez-Parkina J., Turbasa M., Przewlocki R.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr Suppl.1

Models of alcohol drinking in rodents are useful in determining factors underlying uncontrolled alcohol abuse. Here we describe a new model, which overcomes a limitation of previous approaches, the necessity of studying animals in isolation. Over the course of 4–5 weeks group-housed mice intermittently received free or instrumental access to 12% alcohol in the IntelliCage system. Animals developed stable alcohol preference which was similar across 6 cohorts tested (46.6 ± 12.8%). Compared to behaviors of singlehoused mice, we found no escalation of drinking over time, and no difference in alcohol preference between males and females, but comparable levels of alcohol preference to those previously reported. Motivation to obtain alcohol or saccharin measured under a progressive ratio schedule was initially similar, but the breakpoint decreased over consecutive sessions in case of alcohol (from 19.8 to 15.9). Conversely, addition of 0.03% quinine had a smaller impact on alcohol than saccharine intake (72.2% vs. 97.2% decrease). We observed that sequences of animal entries to alcohol-containing corners diverged from random distribution. Thus, this model applied to group-housed mice induces stable levels of alcohol drinking and allows to measure its motivational aspects as well as explore relations between social structure and drinking behavior.

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Long-term morphine self-administration schedule in intellicages as a preclinical model of opioid abuse in mice

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Skupio U., Sikora M., Turbasa M., Przewlocki R.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr Supl.

BACKGROUND AND AIMS: Chronic exposure to opiates induces various alterations in brain physiology that may lead to formation of dependence, tolerance and addiction. Commonly used approaches for modeling morphine dependence involve the use of conditioned place preference, which lacks voluntary intake of the drug, and morphine self-administration, which requires isolating the animals. Here, we describe a novel model of long-term morphine self-administration in C57BL/6J mice. METHODS:We have used IntelliCage (NewBehavior, Switzerland) system to observe the animals without unnecessary experimental intervention. The animals in two separate cages were allowed access to sweetened morphine (0.5 mg/ml) or saccharin solutions for 3 executive months with saccharin concentration being gradually lowered (from 0.2% to 0.02%). We behaviorally challenged animals to test for symptoms of compulsive morphine drinking, using paradigms like saccharin reduction, progressive ratio schedule and intermittent access to rewarding substance. RESULTS: We have observed stable preference to both saccharin and morphine throughout the drinking schedule. The animals performed significantly increased number of instrumental responses to obtain access to the bottle with morphine (progressive ratio schedule) and significantly more nose pokes in attempt to obtain rewarding substance during intermittent access procedure, when compared to saccharin group. What is more, morphine dependent animals exhibited a variety of spontaneous withdrawal symptoms that lasted up to 32 hours. CONCLUSIONS: This study demonstrate that our model reliably leads to stable morphine drinking while avoiding the limitations associated with testing isolated animals. Mice drinking morphine exhibit many of the symptoms of dependence and craving compared to control animals. Therefore, this model may be well suited to screening for the effects of genetic mutations or pharmacological treatments on morphine-induced behaviors.

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Phenotyping reward-driven behaviors in transgenic mice

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Lopata K., Cieslak P. E., Turbasa M., Rodrigez Parkitna J.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 3

The dopamine neurons of the ventral midbrain form the core of the brain’s reward system and the plasticity of these neurons are essential in mediating the effects of positive reinforcement. To study the underlying neuronal mechanisms we used genetically modified mice (NR1DATCreERT2) that lacked NMDA glutamate receptors on dopamine neurons and thus had impaired plasticity on excitatory synapses. We found that mutant mice performed similarly as controls in food-self administration test under fixed, progressive or variable interval schedules. However, NR1DATCreERT2 mice failed to acquire instrumental responding for sensory stimuli in the operant sensation seeking test. Furthermore, when mice were tested for sweet taste preference under instrumental access (FR3) in an IntelliCage, mutants did not prefer the saccharine solution over pure water (52±11%) while control animals reached 98±13% preference. The anhedonia-like phenotype prompted us to test the animals in forced swimming test and we found that NR1DATCreERT2 animals spent more time immobile than controls. In summary, we believe that the loss of NMDA receptors on dopamine neurons caused decreased sensitivity to sensory stimuli, anhedonia and increased learned helplessness, without causing obvious impairments in instrumental learning. Supported by the grant OPUS 2011/03/B/NZ4/02211

Ograniczanie wyników

3 Acta Neurobiologiae Experimentalis

3 Turbasa M.

2 Przewlocki R.

1 Cieslak P. E.

1 Lopata K.

1 Rodrigez Parkitna J.

1 Rodriguez-Parkina J.

1 Sikora M.

1 Skupio U.

1 Smutek M.

1 2015

1 2014

1 2013

Alcohol drinking under intermittent access in group-housed C57BL/6J mice

Long-term morphine self-administration schedule in intellicages as a preclinical model of opioid abuse in mice

Phenotyping reward-driven behaviors in transgenic mice