CRF type 1 receptor antagonism in ventral tegmental area of adolescent rats during social defeat: prevention of escalated cocaine self-administration in adulthood and behavioral adaptations during adolescence
Autor: | Klaus A. Miczek, Joseph F. DeBold, Andrew R. Burke |
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Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine endocrine system Corticotropin-Releasing Hormone Aminopyridines Self Administration Cocaine related disorders medicine.disease_cause Receptors Corticotropin-Releasing Hormone Article Social defeat Cocaine-Related Disorders 03 medical and health sciences Corticotropin-releasing hormone 0302 clinical medicine Cocaine Adaptation Psychological medicine Animals Psychological stress Rats Long-Evans Social Behavior Receptor Pharmacology Ventral Tegmental Area Rats Behavior Addictive Ventral tegmental area Disease Models Animal 030104 developmental biology medicine.anatomical_structure Self-administration Antagonism Psychology Reinforcement Psychology Neuroscience Locomotion Stress Psychological hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery |
Zdroj: | Psychopharmacology. 233:2727-2736 |
ISSN: | 1432-2072 0033-3158 |
Popis: | Activation of corticotropin-releasing factor type 1 receptors (CRF-R1) in the ventral tegmental area (VTA) represents a critical mechanism for social defeat to escalate cocaine self-administration in adult rats.We determined the acute effect of a CRF-R1 antagonist (CP376395) microinfusion into the VTA prior to each episode of social defeat in adolescent rats and determined whether this drug treatment could prevent later escalation of cocaine taking in early adulthood.Rats were implanted with bilateral cannulae aimed at the VTA 5 days before the first social defeat. Bilateral microinfusion of CP376395 (500 ng/side) or vehicle occurred 20 min before each episode of social defeat on postnatal days (P) 35, 38, 41, and 44. Behavior was quantified on P35 and P44. On P57, rats were implanted with intra-jugular catheters, and subsequent cocaine self-administration was analyzed.CP376395-treated adolescent rats walked less and were attacked more slowly but were socially investigated more than vehicle-treated adolescents. Vehicle-treated rats showed increased social and decreased non-social exploration from P35 to P44, while CP376395-treated rats did not. Socially defeated, vehicle-treated adolescents took more cocaine during a 24-h unlimited access binge during adulthood. The latency to supine posture on P44 was inversely correlated with later cocaine self-administration during fixed and progressive ratio schedules of reinforcement and during the binge.CP376395 treatment in adolescence blocked escalation of cocaine taking in adulthood. Episodes of social defeat stress engender neuroadaptation in CRF-R1s in the VTA that alter coping with social stress and that persist into adulthood. |
Databáze: | OpenAIRE |
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