Antagonism of the kappa opioid receptor attenuates THC-induced place aversions in adult male Sprague-Dawley rats. 2017

Matthew M Clasen, and Shaun M Flax, and Briana J Hempel, and Kejun Cheng, and Kenner C Rice, and Anthony L Riley
Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, Washington, DC 20016, USA. Electronic address: mc0817a@student.american.edu.

BACKGROUND Prior research with transgenic mice in which the kappa opioid receptor (KOR) has been suppressed or activated suggests that the aversive effects of THC are mediated by activity of this receptor subtype. If the activity of the KOR system is responsible for mediating the THC's aversive effects, then selective antagonism of the KOR by norBNI should block such aversive effects. To test this hypothesis, rats were pretreated with norBNI 24h prior to place conditioning with THC to assess its effect on the acquisition of THC-induced place aversions. METHODS In Experiment 1, rats pretreated with norBNI (0 or 15mg/kg) were exposed 24h later to one side of a place conditioning chamber and injected with THC (0, 0.56, 1 and 3.2mg/kg). On the next day, they were injected with vehicle and placed on the opposite side of the chamber. This was repeated for a total of five cycles followed by a test of the animal's aversion to the THC-paired side. In Experiment 2, rats were pretreated with norBNI (0 or 30mg/kg) prior to place conditioning 24h later with THC (0 or 3.2mg/kg). RESULTS In Experiment 1, THC produced dose-dependent place aversions that were unaffected by norBNI (15mg/kg). In Experiment 2, THC induced significant place aversions that were fully attenuated by norBNI (30mg/kg). CONCLUSIONS Although 15mg/kg norBNI was ineffective in antagonizing the aversive effects of THC, 30mg/kg norBNI blocked the ability of THC to induce a place aversion. The results of the latter assessment are consistent with prior research with transgenic manipulations of the KOR and provide further evidence for the role of the KOR system in the aversive properties of THC.

UI MeSH Term Description Entries
D008297 Male Males
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001362 Avoidance Learning A response to a cue that is instrumental in avoiding a noxious experience. Aversion Behavior,Aversion Learning,Aversive Behavior,Aversive Learning,Avoidance Behavior,Aversion Behaviors,Aversive Behaviors,Avoidance Behaviors,Behavior, Aversion,Behavior, Aversive,Behavior, Avoidance,Behaviors, Aversion,Behaviors, Aversive,Behaviors, Avoidance,Learning, Aversion,Learning, Aversive,Learning, Avoidance
D013759 Dronabinol A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. THC,Tetrahydrocannabinol,delta(9)-THC,9-ene-Tetrahydrocannabinol,Marinol,Tetrahydrocannabinol, (6a-trans)-Isomer,Tetrahydrocannabinol, (6aR-cis)-Isomer,Tetrahydrocannabinol, (6aS-cis)-Isomer,Tetrahydrocannabinol, Trans-(+-)-Isomer,Tetrahydrocannabinol, Trans-Isomer,delta(1)-THC,delta(1)-Tetrahydrocannabinol,delta(9)-Tetrahydrocannabinol,9 ene Tetrahydrocannabinol,Tetrahydrocannabinol, Trans Isomer
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017473 Receptors, Opioid, kappa A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins. Opioid Receptors, kappa,Receptors, kappa,Receptors, kappa Opioid,kappa Receptors,kappa Opioid Receptor,kappa Receptor,Opioid Receptor, kappa,Receptor, kappa,Receptor, kappa Opioid,kappa Opioid Receptors
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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