Suppression of Methamphetamine Self-Administration by Ketamine
Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat
Model of Schizophrenia

J 2017

Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia

RUDÁ, Jana, Zuzana BABINSKÁ, Tibor ŠTARK and Vincenzo MICALE

Basic information

Original name

Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia

Authors

RUDÁ, Jana (203 Czech Republic, guarantor, belonging to the institution), Zuzana BABINSKÁ (703 Slovakia, belonging to the institution), Tibor ŠTARK (703 Slovakia, belonging to the institution) and Vincenzo MICALE (380 Italy, belonging to the institution)

Edition

Neurotoxicity research, New York, Springer, 2017, 1029-8428

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.186

RIV identification code

RIV/00216224:14110/17:00097261

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s12640-017-9718-9

UT WoS

000403591600013

Keywords in English

Ketamine; MAM model; Methamphetamine; Self-administration; Sprague-Dawley rats

Abstract

V originále

Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration. MAM was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor activity test and later IV self-administration (IVSA) were then performed in the male offspring followed by a period of forced abstinence and relapse of METH taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg) was administered intraperitoneally 30 min prior to the self-administration session. As documented previously, the MAM rats showed a lack of habituation in the locomotor activity test but developed stable maintenance of METH self-administration with no difference in operant behaviour to control animals. Results show that ketamine treatment significantly reduced the METH intake in the control animals but not in MAM animals. Ketamine effect on METH self-administration may be explained by increased glutamatergic signalling in the prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition of GABA interneurons which was shown to be impaired in the MAM rats. This mechanism may at least partly explain the clinically proven anti-craving potential of ketamine and allow development of more specific anti-craving medications with fewer risks.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1063/2016, interní kód MU

Name: Experimentální a translační farmakologický výzkum a vývoj

Investor: Masaryk University, Category A

ROZV/24/LF/2016, interní kód MU

Name: LF - Příspěvek IP 2016

Investor: Ministry of Education, Youth and Sports of the CR

3SGA5789, interní kód MU

Name: PRECIPITATION OF SCHIZOPHRENIA-LIKE PHENOTYPE BY PRENATAL INFLUENCES: ASSESSING THE ROLE OF THE ENDOCANNABINOID SYSTEM (Acronym: ncRNAPain)

Investor: South-Moravian Region, Incoming grants

Citovat

RUDÁ, Jana, Zuzana BABINSKÁ, Tibor ŠTARK and Vincenzo MICALE. Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia. Neurotoxicity research. New York: Springer, 2017, vol. 32, No 1, p. 121-133. ISSN 1029-8428. Available from: https://dx.doi.org/10.1007/s12640-017-9718-9.

@article{1386449,
   author = {Rudá, Jana and Babinská, Zuzana and Štark, Tibor and Micale, Vincenzo},
   article_location = {New York},
   article_number = {1},
   doi = {http://dx.doi.org/10.1007/s12640-017-9718-9},
   keywords = {Ketamine; MAM model; Methamphetamine; Self-administration; Sprague-Dawley rats},
   language = {eng},
   issn = {1029-8428},
   journal = {Neurotoxicity research},
   title = {Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia},
   volume = {32},
   year = {2017}
}

TY  - JOUR
ID  - 1386449
AU  - Rudá, Jana - Babinská, Zuzana - Štark, Tibor - Micale, Vincenzo
PY  - 2017
TI  - Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia
JF  - Neurotoxicity research
VL  - 32
IS  - 1
SP  - 121-133
EP  - 121-133
PB  - Springer
SN  - 10298428
KW  - Ketamine
KW  - MAM model
KW  - Methamphetamine
KW  - Self-administration
KW  - Sprague-Dawley rats
N2  - Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration. MAM was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor activity test and later IV self-administration (IVSA) were then performed in the male offspring followed by a period of forced abstinence and relapse of METH taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg) was administered intraperitoneally 30 min prior to the self-administration session. As documented previously, the MAM rats showed a lack of habituation in the locomotor activity test but developed stable maintenance of METH self-administration with no difference in operant behaviour to control animals. Results show that ketamine treatment significantly reduced the METH intake in the control animals but not in MAM animals. Ketamine effect on METH self-administration may be explained by increased glutamatergic signalling in the prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition of GABA interneurons which was shown to be impaired in the MAM rats. This mechanism may at least partly explain the clinically proven anti-craving potential of ketamine and allow development of more specific anti-craving medications with fewer risks.
ER  -

RUDÁ, Jana, Zuzana BABINSKÁ, Tibor ŠTARK and Vincenzo MICALE. Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia. \textit{Neurotoxicity research}. New York: Springer, 2017, vol.~32, No~1, p.~121-133. ISSN~1029-8428. Available from: https://dx.doi.org/10.1007/s12640-017-9718-9.

Detailed Information on Publication Record