Context-Specific Tolerance and Pharmacological Changes in the Infralimbic Cortex-Nucleus Accumbens Shell Pathway Evoked by Ketamine

Author(s)

Silva-Cardoso, Gleice Kelli ^[1] ; Nobre, Manoel Jorge ^{[2, 1]}

Affiliation

^[1] Univ Sao Paulo, Lab Psicobiol, Dept Psicol, Fac Filosofia Ciencias & Letras Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Uni FACEF, Dept Psicol, BR-14401135 Franca, SP - Brazil

• Document type: Journal article
• Source: Neurochemical Research; v. 46, n. 7 MAR 2021.
• Web of Science Citations: 0

Abstract

Like other drugs, ketamine is abused due to its ability to act as a positive reinforcer in the control of behavior, just as natural reinforcers do. Besides, through Pavlovian conditioning, tolerance to drug effects can become conditioned to specific contextual cues showing that environmental stimuli can act as powerful mediators of craving and relapse. In the present study, we shall investigate the effects of long-term ketamine administration and withdrawal on behavioral measures and emotionality, the drug-context-specific influence on the tolerance to the sedative effects of an anesthetic dose of ketamine, and the neuropharmacological events underlying this phenomenon, in rats conditioned with 10 mg/kg of ketamine and later challenged with a dose of ketamine of 80 mg/kg in a familiar and non-familiar environment. Variations in dopamine and serotonin efflux in the infralimbic cortex-nucleus accumbens shell circuitry (IL-NAcSh) was further recorded in the same conditions. Our results highlight that besides its well-known reinforcing properties, ketamine also shares the ability to induce behavioral and pharmacological conditioned tolerance, associated with increases in cortical (IL), and decreases in striatal (NAcSh) dopamine release. To our knowledge, we are presenting the first set of behavioral and neurochemical data showing that, like other drugs of abuse, ketamine can induce learned context-specific tolerance. (AU)

• FAPESP's process: 15/17568-5 - Changes on cortical neurochemistry associated with the expression of contextual conditioned tolerance of rats submitted to chronic treatment with the dissociative anesthetic ketamine
• Grantee: Gleice Kelli Ribeiro da Silva Cardoso
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/18268-0 - An assay on the behavioral, neuropharmacological, and neurobiological changes induced by chronic ketamine in neural systems related to the auditory sensory processing.
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/23690-5 - Behavioral, psychophysiological and neurochemical changes underlying withdrawal from chronic treatment with the dissociative anesthetic ketamine
• Grantee: Manoel Jorge Nobre Do Espirito Santo
• Support Opportunities: Regular Research Grants