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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Neurochemical Research; v. 46, n. 7 MAR 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/17568-5 - Alterações neuroquímicas em sistemas subcorticais subjacentes à expressão da tolerância condicionada ao contexto em ratos submetidos à administração crônica do anestésico dissociativo ketamina
• Beneficiário: Gleice Kelli Ribeiro da Silva Cardoso
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 17/18268-0 - Análise das alterações comportamentais, neurofarmacológicas e neurofisiológicas em sistemas neurais relacionados à percepção e processamento da informação sensorial auditiva, induzidas pela administração crônica do anestésico dissociativo Ketamina.
• Beneficiário: Manoel Jorge Nobre Do Espirito Santo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/23690-5 - Alterações comportamentais, psicofisiológicas e neuroquímicas subjacentes aos efeitos da interrupção da administração crônica do anestésico dissociativo ketamina
• Beneficiário: Manoel Jorge Nobre Do Espirito Santo
• Modalidade de apoio: Auxílio à Pesquisa - Regular