Early-life ketamine exposure attenuates the preference for ethanol in adolescent Sprague-Dawley rats.

Abstract:

:Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces quick and effective antidepressant results in depressed juvenile and adult individuals. The long-term consequences of using ketamine in juvenile populations are not well known, particularly as it affects vulnerability to drugs of abuse later in life, given that ketamine is also a drug of abuse. Thus, the current study examined whether early-life ketamine administration produces long-term changes in the sensitivity to the rewarding effects of ethanol, as measured using the conditioned place preference (CPP) paradigm. On postnatal day (PD) 21, juvenile male and female rats were pretreated with ketamine (0.0 or 20 mg/kg) for 10 consecutive days (i.e., PD 21-30) and then evaluated for ethanol-induced CPP (0.0, 0.125, 0.5, or 2.0 g/kg) from PD 32-39. Results revealed that early-life ketamine administration attenuated the rewarding properties of ethanol in male rats, as ketamine pretreated rats failed to exhibit ethanol-induced CPP at any dose compared to saline pretreated rats, which showed an increased preference towards the ethanol-paired compartment in a dose-dependent manner. In females, ethanol-induced CPP was generally less robust compared to males, but ketamine pretreatment resulted in a rightward shift in the dose-response curve, given that ketamine pretreated rats needed a higher dose of ethanol compared to saline pretreated rats to exhibit ethanol-induced CPP. When considered together, the findings suggest that early use of ketamine does not appear to enhance the vulnerability to ethanol later in life, but in contrast, it may attenuate the rewarding effects of ethanol.

journal_name

Behav Brain Res

authors

Franco D,Zamudio J,Blevins KM,Núñez-Larios EA,Ricoy UM,Iñiguez SD,Zavala AR

doi

10.1016/j.bbr.2020.112626

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

112626

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(20)30325-9

journal_volume

389

pub_type

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