Attenuation of the anxiogenic effects of cocaine by 5-HT1B autoreceptor stimulation in the bed nucleus of the stria terminalis of rats

Autor: Anand S. Patil, Lucy Zhou, Carl Provenzano, Dylan R. Flanagan, Michael A. Brito, Sayeh Akhavan, Adam K. Klein, Aaron Ettenberg, Erin M. Purvis, Nikki Le, Tatum Ohana, Alex Wei
Rok vydání: 2017
Předmět:
Male
Pyridines
5-HT
Self Administration
Pharmacology
Anxiety
Medical and Health Sciences
Substance Misuse
0302 clinical medicine
Cocaine
Dopamine Uptake Inhibitors
Autoreceptors
Psychiatry
Septal nuclei
Operant runway
Self-administration
medicine.anatomical_structure
Autoreceptor
Locomotion
Receptor
Agonist
Serotonin
Drug aversion
medicine.drug_class
Morpholines
Drug-Seeking Behavior
Drug reward
Serotonin 5-HT1 Receptor Antagonists
Serotonergic
Drug abuse
Basic Behavioral and Social Science
03 medical and health sciences
Dorsal raphe nucleus
Extended amygdala
Behavioral and Social Science
medicine
Animals
Benzopyrans
Motivation
business.industry
Psychology and Cognitive Sciences
Neurosciences
030227 psychiatry
Rats
Brain Disorders
Stria terminalis
Anxiogenic
Septal Nuclei
Sprague-Dawley
5-HT1B
business
Drug Abuse (NIDA only)
Neuroscience
030217 neurology & neurosurgery
Zdroj: Psychopharmacology, vol 234, iss 3
Popis: RationaleCocaine produces significant aversive/anxiogenic actions whose underlying neurobiology remains unclear. A possible substrate contributing to these actions is the serotonergic (5-HT) pathway projecting from the dorsal raphé (DRN) to regions of the extended amygdala, including the bed nucleus of the stria terminalis (BNST) which have been implicated in the production of anxiogenic states.ObjectivesThe present study examined the contribution of 5-HT signaling within the BNST to the anxiogenic effects of cocaine as measured in a runway model of drug self-administration.MethodsMale Sprague-Dawley rats were fitted with bilateral infusion cannula aimed at the BNST and then trained to traverse a straight alley once a day for a single 1mg/kg i.v. cocaine infusion delivered upon goal-box entry on each of 16 consecutive days/trials. Intracranial infusions of CP 94,253 (0, 0.25, 0.5, or 1.0μg/side) were administered to inhibit local 5-HT release via activation of 5-HT1B autoreceptors. To confirm receptor specificity, the effects of this treatment were then challenged by co-administration of the selective 5-HT1B antagonist NAS-181.ResultsIntra-BNST infusions of the 5-HT1B autoreceptor agonist attenuated the anxiogenic effects of cocaine as reflected by a decrease in runway approach-avoidance conflict behavior. This effect was reversed by the 5-HT1B antagonist. Neither start latencies (a measure of the subject's motivation to seek cocaine) nor spontaneous locomotor activity (an index of motoric capacity) were altered by either treatment.ConclusionsInhibition of 5-HT1B signaling within the BNST selectively attenuated the anxiogenic effects of cocaine, while leaving unaffected the positive incentive properties of the drug.
Databáze: OpenAIRE
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