Presentation Title

Ketamine Exposure during Adolescence Increases Sensitivity To Reward-related Stimuli in Adulthood

Author(s) Information

Mirella Hernandez

Presentation Type

Poster Presentation/Art Exihibt

College

College of Social and Behavioral Sciences

Major

Biology

Psychology

Location

Event Center A & B

Faculty Mentor

Dr. Sergio Iniguez

Start Date

5-19-2016 1:00 PM

End Date

5-19-2016 2:30 PM

Abstract

Pediatric depression was not well recognized until relatively recent. Today, however, major depressive disorder (MDD) is commonly diagnosed in children and adolescents, and when left untreated, may result in negative consequences that extend into adulthood. It is estimated that children and adolescents who suffer from MDD are likely to develop conduct and anxiety disorders, and that up to 25% eventually develop substance abuse disorder. Consequently, this has resulted in a disproportionate increase in the prevalence of antidepressants prescribed to populations below 20 years of age. Recently, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, has been shown to alleviate symptoms of MDD in individuals that suffer from treatment-resistant depression. However, little is known about the potential long-term consequences of exposure to ketamine during early development. This is particularly important to examine, given ket amine’s abuse potential. To address this issue at the preclinical level, we examined whether ketamine exposure during adolescence results in long-lasting changes in sensitivity to the rewarding effects of sucrose (i.e., natural reward), as well as cocaine (i.e., drug reward). Specifically, male c57BL/6 mice were exposed to ketamine (0 or 20 mg/ kg) during adolescence (postnatal days [PD] 35-49) and were later assessed in adulthood (PD 70+) on behavioral responsivity to a sucrose solution (1%), or cocaine (0, 2.5, 5, 7.5, 10, or 20 mg/kg) place conditioning (CPP). Here we show that adult mice pretreated with ketamine during adolescence displayed enhanced preference for a sucrose solution, as well as environments previously paired with moderately low doses of cocaine, when compared to saline pre-treated controls. Together, our findings suggest that exposure to ketamine during adolescence increases sensitivity to both natural and drug-rewards, later in life.

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May 19th, 1:00 PM May 19th, 2:30 PM

Ketamine Exposure during Adolescence Increases Sensitivity To Reward-related Stimuli in Adulthood

Event Center A & B

Pediatric depression was not well recognized until relatively recent. Today, however, major depressive disorder (MDD) is commonly diagnosed in children and adolescents, and when left untreated, may result in negative consequences that extend into adulthood. It is estimated that children and adolescents who suffer from MDD are likely to develop conduct and anxiety disorders, and that up to 25% eventually develop substance abuse disorder. Consequently, this has resulted in a disproportionate increase in the prevalence of antidepressants prescribed to populations below 20 years of age. Recently, the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, has been shown to alleviate symptoms of MDD in individuals that suffer from treatment-resistant depression. However, little is known about the potential long-term consequences of exposure to ketamine during early development. This is particularly important to examine, given ket amine’s abuse potential. To address this issue at the preclinical level, we examined whether ketamine exposure during adolescence results in long-lasting changes in sensitivity to the rewarding effects of sucrose (i.e., natural reward), as well as cocaine (i.e., drug reward). Specifically, male c57BL/6 mice were exposed to ketamine (0 or 20 mg/ kg) during adolescence (postnatal days [PD] 35-49) and were later assessed in adulthood (PD 70+) on behavioral responsivity to a sucrose solution (1%), or cocaine (0, 2.5, 5, 7.5, 10, or 20 mg/kg) place conditioning (CPP). Here we show that adult mice pretreated with ketamine during adolescence displayed enhanced preference for a sucrose solution, as well as environments previously paired with moderately low doses of cocaine, when compared to saline pre-treated controls. Together, our findings suggest that exposure to ketamine during adolescence increases sensitivity to both natural and drug-rewards, later in life.