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
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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