Responses to drugs of abuse and non-drug rewards in leptin deficient ob/ob mice. Psychopharmacology (Berl) 2016 Jul;233(14):2799-811
Date
06/04/2016Pubmed ID
27256358Pubmed Central ID
PMC5095929DOI
10.1007/s00213-016-4323-9Scopus ID
2-s2.0-84976439458 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
RATIONALE: Although leptin receptors are found in hypothalamic nuclei classically associated with homeostatic feeding mechanisms, they are also present in brain regions known to regulate hedonic-based feeding, natural reward processing, and responses to drugs of abuse. The ob/ob mouse is deficient in leptin signaling, and previous work has found altered mesolimbic dopamine signaling and sensitivity to the locomotor activating effects of amphetamine in these mice.
OBJECTIVES: We directly assessed responses to three drugs of abuse and non-drug rewards in the leptin-deficient ob/ob mouse.
METHODS: Ob/ob mice were tested in assays of sweet preference, novelty seeking, and drug reward/reinforcement.
RESULTS: In assays of novelty seeking, novel open field activity and operant sensation seeking were reduced in ob/ob mice, although novel object interaction and novel environment preference were comparable to wild types. We also found that ob/ob mice had specific phenotypes in regard to cocaine: conditioned place preference for 2.5 mg/kg was increased, while the locomotor response to 10 mg/kg was reduced, and cocaine self-administration was the same as wild types. Ob/ob mice also acquired self-administration of the potent opioid remifentanil, but breakpoints for the drug were significantly reduced. Finally, we found significant differences in ethanol drinking in ob/ob mice that correlated negatively with body weight and positively with operant sensation seeking.
CONCLUSIONS: In conclusion, ob/ob mice displayed task-specific deficits in novelty seeking and dissociable differences in reward/reinforcement associated with cocaine, remifentanil, and ethanol.
Author List
Muelbl MJ, Nawarawong NN, Clancy PT, Nettesheim CE, Lim YW, Olsen CMAuthor
Christopher M. Olsen PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmphetamineAnimals
Behavior, Animal
Central Nervous System Depressants
Cocaine
Conditioning, Operant
Disease Models, Animal
Dopamine Uptake Inhibitors
Ethanol
Exploratory Behavior
Feeding Behavior
Leptin
Locomotion
Male
Mice
Motor Activity
Piperidines
Taste
