CGP 44532, a GABAB receptor agonist, is hedonically neutral and reduces cocaine-induced enhancement of reward.
Drugs that alter the function of gamma-aminobutyric acid (GABA) neurotransmission seem to reduce cocaine reinforcement, and as such may be useful in pharmacologically treating cocaine addiction. In the present experiment, the anti-cocaine effects of CGP 44532, a phosphinic acid analogue of GABA, and a highly selective GABA(B) receptor agonist were examined in male Sprague-Dawley rats using brain stimulation reward (BSR) paradigm. In this method, the relationship between the rate of bar pressing and the frequency of stimulation pulses was analyzed in two measures: the maximum rate of responding (MAX) and the frequency necessary to sustain half maximal rate of responding known as the locus of rise (LOR). CGP 44532 was found to be hedonically neutral without producing any measurable effects on performance (MAX). It also dose-dependently reduced cocaine-induced BSR enhancement, in the order of 15-31%, as shown by progressive shifts in LOR towards baseline. Thus, in theory, administration of CGP 44532 might reduce cocaine's hedonic effects, while also maintaining patient compliance. Whether this agent would also be effective at curbing craving, a long-term consequence of drug abuse, remains to be determined.
Dobrovitsky
V
V
Department of Psychology & Program in Neuroscience, Northeastern University, Boston, MA 02115, USA.
Pimentel
P
P
Duarte
A
A
Froestl
W
W
Stellar
J R
JR
Trzcińska
M
M
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D063065:Organophosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D010721:Phosphinic Acids; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012201:Reward; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives
C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; D018765:Dopamine Uptake Inhibitors; D063065:Organophosphonates; D010721:Phosphinic Acids; D005680:gamma-Aminobutyric Acid; D003042:Cocaine