Suppressing effect of the novel positive allosteric modulator of the GABAB receptor, COR659, on locomotor hyperactivity induced by different drugs of abuse.

Abstract:

:COR659 is a recently synthesized positive allosteric modulator (PAM) of the GABAB receptor. Similarly to all GABAB PAMs tested to date, COR659 has been reported to suppress different alcohol-related behaviors in rodents. The present study was designed to assess whether the anti-addictive properties of COR659 extend to drugs of abuse other than alcohol. Specifically, it investigated the effect of COR659 on cocaine-, amphetamine-, nicotine-, and morphine-induced locomotor hyperactivity in mice. To this aim, independent groups of CD1 mice were acutely pretreated with COR659 (0, 10, and 20 mg/kg; i.p.), then acutely treated with cocaine (0 and 10 mg/kg, s.c.), amphetamine (0 and 5 mg/kg; s.c.), nicotine (0 and 0.05 mg/kg; s.c.), or morphine (0 and 20 mg/kg; s.c.), and finally exposed for 60 min to a photocell-equipped motility cage. When given alone, both doses of COR659 were ineffective on spontaneous locomotor activity. Pretreatment with COR659 reduced, or even suppressed, the increase in motility counts induced by cocaine, amphetamine, nicotine, and morphine. Since locomotor hyperactivity is an attribute common to drugs of abuse, the results of the present study constitute the first line of evidence on the extension of the preclinical, anti-addictive profile of COR659 to cocaine, amphetamine, nicotine, and morphine.

journal_name

Behav Brain Res

authors

Lobina C,Maccioni P,Lorrai I,Zaru A,Collu M,Carai MAM,Brizzi A,Mugnaini C,Gessa GL,Corelli F,Colombo G

doi

10.1016/j.bbr.2020.113045

subject

Has Abstract

pub_date

2021-02-26 00:00:00

pages

113045

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(20)30744-0

journal_volume

400

pub_type

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