The role of beta-endorphin in the acute motor stimulatory and rewarding actions of cocaine in mice.
BACKGROUND
Opioid receptor antagonists have been shown to attenuate the rewarding and addictive effects of cocaine. Furthermore, cocaine has been shown to cause the release of beta-endorphin, an endogenous opioid peptide.


OBJECTIVE
We assessed whether this neuropeptide would play a functional role in cocaine-induced motor stimulation and conditioned place preference (CPP).


METHODS
Mice lacking beta-endorphin and their wild-type littermates were habituated to motor activity chambers for 1 h, then injected with cocaine (0, 15, 30, or 60 mg/kg, intraperitoneally) or morphine (0, 5, or 10 mg/kg, subcutaneously), and motor activity was recorded for 1 h. In the CPP paradigm, mice were tested for baseline place preference on day 1. On days 2 and 3, mice received an alternate-day saline/cocaine (15, 30, or 60 mg/kg) or saline/morphine (10 mg/kg) conditioning session and then tested for postconditioning place preference on day 4.


RESULTS
Cocaine-induced motor stimulation and CPP were both reduced in mice lacking beta-endorphin. On the other hand, motor stimulation and CPP induced by morphine were not altered in mutant mice.


CONCLUSIONS
The present results demonstrate that the endogenous opioid peptide beta-endorphin plays a modulatory role in the motor stimulatory and rewarding actions of acute cocaine.
Marquez
Paul
P
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766, USA.
Baliram
Ramkumarie
R
Dabaja
Ibrahim
I
Gajawada
Nagaraju
N
Lutfy
Kabirullah
K
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003433:Crosses, Genetic; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006580:Genetic Carrier Screening; D005838:Genotype; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009020:Morphine / Q000494:pharmacology; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012201:Reward; D012931:Social Environment; D001615:beta-Endorphin / Q000235:genetics / Q000502:physiology*
D018765:Dopamine Uptake Inhibitors; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D009020:Morphine; D003042:Cocaine