6533b7d2fe1ef96bd125ea90

RESEARCH PRODUCT

Effects of CGS 10746B on hyperactivity and place preference induced by morphine

Carmen ManzanedoJosé MiñarroMarta Rodríguez-ariasMaría A. AguilarAmparo Serrano

subject

Malemedicine.medical_specialtyThiazepinesDopamineConditioning ClassicalMale miceMice Inbred StrainsSocial EnvironmentChoice BehaviorMiceBehavioral Neurosciencechemistry.chemical_compoundDopamineInternal medicinemedicineAnimalsDrug InteractionsNeurotransmitterDose-Response Relationship DrugMorphineChemistryAssociation LearningBrainConditioned place preferenceDose–response relationshipEndocrinologyMorphineCatecholamineConditioningNeuroscienceAntipsychotic Agentsmedicine.drug

description

The effects of CGS 10746B, a dopamine release inhibitor, on spontaneous locomotor activity, morphine-induced hyperactivity, acquisition of conditioned place paradigm and morphine-induced conditioned place preference (CPP) was evaluated in male mice. In experiment 1, animals treated with CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 2, 4, 8, 16, 24 and 32 mg/kg) were placed in an actimeter during a period of 90 min. In experiment 2, animals treated with CGS 10746B (0.5, 1, 3 and 10 mg/kg), morphine (40 mg/kg) or morphine (40 mg/kg) plus CGS 10746B (0.5, 1, 3 and 10 mg/kg) were conditioned following a procedure unbiased in terms of initial spontaneous preference. In experiment 1, it was found that a decrease in spontaneous locomotor activity was produced between 0 and 45 min after administration of 24 and 32 mg/kg of CGS 10746B. In contrast, morphine induced hyperactivity between 45 and 90 min after administration. CGS 10746B reduced morphine-induced hyperactivity with doses of 2 mg/kg and higher. In experiment 2, CGS 10746B did not produce any effect on place conditioning but blocked morphine-induced CPP with doses from 1 mg/kg upwards. Our results confirm that an intact dopamine neurotransmission is critical for the manifestation of the motor and place preference conditioning effects of morphine.

https://doi.org/10.1016/s0166-4328(01)00237-6