PMID- 30448991
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20200225
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 236
IP  - 3
DP  - 2019 Mar
TI  - Effects of cocaine on the discriminative stimulus and reinforcing effects of 
      mephedrone in male rats.
PG  - 1043-1056
LID - 10.1007/s00213-018-5110-6 [doi]
AB  - RATIONALE: Abuse of cathinones has been a worldwide health concern for some time. 
      Their chemical structures and wide variation in pharmacodynamic effects have led 
      to clinical and preclinical effects that can be both similar to and different 
      from other psychoactive substances such as methylenedioxymethamphetamine (MDMA), 
      methamphetamine, and cocaine. OBJECTIVE: The present study examined the 
      discriminative stimulus and reinforcing effects of mephedrone to further 
      characterize the behavioral and pharmacological profile of this first-generation 
      substituted methcathinone. METHODS: Rats were trained to discriminate mephedrone 
      (3.2 mg/kg) from saline under a fixed-ratio 20 (FR-20) schedule of food 
      presentation. After establishing dose-effect curves for increasing cumulative 
      doses of mephedrone, substitution tests were conducted with bupropion 
      (5.6-32 mg/kg), cocaine (1.8-18 mg/kg), morphine (0.56-10 mg/kg), and 
      amitriptyline (3.2-32 mg/kg). In addition, cocaine (3.2-18 mg/kg) and the 
      serotonin type-2 (5-HT2) receptor antagonist ritanserin (1, 3.2, and 10 mg/kg) 
      were administered prior to the cumulative doses of mephedrone. Lastly, varying 
      infusion doses of cocaine were substituted for mephedrone in subjects trained to 
      self-administer mephedrone, and varying infusion doses of mephedrone were 
      substituted for cocaine in subjects trained to self-administer cocaine to assess 
      the importance of drug history on the reinforcing effects of mephedrone. RESULTS: 
      Of the drugs tested, cocaine had the highest level of mephedrone-lever responding 
      when administered alone (73.5%). In combination with mephedrone, cocaine shifted 
      the mephedrone dose-effect curve upwards in an infra-additive manner. Ritanserin 
      had a small, but non-significant, effect on mephedrone's discriminative stimulus 
      effects. An extensive history (baseline) of cocaine self-administration increased 
      mephedrone self-administration compared to that obtained in mephedrone-trained 
      subjects, whereas a baseline of mephedrone self-administration decreased cocaine 
      self-administration compared to that obtained in cocaine-trained subjects. 
      CONCLUSION: The similarity between the discriminative stimulus effects of cocaine 
      and mephedrone in male rats suggests an important overlap and the relative 
      importance of the dopamine (DAT) and serotonin (SERT) transporters. The 
      self-administration data suggest that mephedrone is less reinforcing than 
      cocaine, but that a history of responding for cocaine can increase the 
      reinforcing effects of mephedrone.
FAU - Erwin, Laura L
AU  - Erwin LL
AUID- ORCID: 0000-0001-6638-6186
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, LA, 70112, USA. 
      lerwin@lsuhsc.edu.
FAU - Nilges, Mark R
AU  - Nilges MR
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, LA, 70112, USA.
FAU - Bondy, Zachary B
AU  - Bondy ZB
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, LA, 70112, USA.
FAU - Winsauer, Peter J
AU  - Winsauer PJ
AD  - Department of Pharmacology and Experimental Therapeutics, Louisiana State 
      University Health Sciences Center, New Orleans, LA, 70112, USA.
AD  - Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health 
      Sciences Center, New Orleans, LA, 70112, USA.
LA  - eng
PT  - Journal Article
DEP - 20181117
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (Illicit Drugs)
RN  - 44RAL3456C (Methamphetamine)
RN  - 8BA8T27317 (mephedrone)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Cocaine/*administration & dosage
MH  - Conditioning, Operant/drug effects/physiology
MH  - Discrimination Learning/*drug effects/physiology
MH  - Dopamine Uptake Inhibitors/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Illicit Drugs/*pharmacology
MH  - Male
MH  - Methamphetamine/administration & dosage/*analogs & derivatives
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - *Reinforcement, Psychology
MH  - Self Administration
OTO - NOTNLM
OT  - Bupropion
OT  - Cocaine
OT  - Drug discrimination
OT  - Drug history
OT  - Mephedrone
OT  - Rats
OT  - Self-administration
OT  - Synthetic cathinone
EDAT- 2018/11/19 06:00
MHDA- 2019/08/28 06:00
CRDT- 2018/11/19 06:00
PHST- 2018/06/26 00:00 [received]
PHST- 2018/11/05 00:00 [accepted]
PHST- 2018/11/19 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2018/11/19 06:00 [entrez]
AID - 10.1007/s00213-018-5110-6 [pii]
AID - 10.1007/s00213-018-5110-6 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2019 Mar;236(3):1043-1056. doi: 
      10.1007/s00213-018-5110-6. Epub 2018 Nov 17.