Effect of gabapentin-like compounds on development and maintenance of morphine-induced conditioned place preference.
BACKGROUND
Psychological dependence to the opioid analgesic morphine is attributable to the rewarding properties of the drug, and its evolution can be divided into two distinct phases: development and maintenance. Both phases can be studied using conditioned place preference (CPP).


OBJECTIVE
To determine whether the two phases can be influenced by pre-treatment with gabapentin-like compounds.


METHODS
CPP to morphine was used to demonstrate the rewarding properties of morphine in the presence or absence of gabapentin-like compounds. In-vivo microdialysis in the nucleus accumbens was used to determine the effects of gabapentin or pregabalin on morphine-induced dopamine release.


RESULTS
Pretreatment with either gabapentin (10-100 mg/kg p.o.) or pregabalin (3-30 mg/kg p.o.) attenuated CPP induced by a submaximal dose of morphine (0.75 mg/kg). Neither gabapentin nor pregabalin had any effect alone in the CPP test. Both gabapentin-like compounds blocked the effect of morphine (0.75 mg/kg s.c.) to increase the release of dopamine in the nucleus accumbens. Studies of the maintenance of CPP to morphine showed CPP was maintained for at least 4 days after the initial test. In a second experiment, it was found that pregabalin (injected once, 24 h after CPP had been demonstrated) was able to reverse morphine-induced CPP.


CONCLUSIONS
Neither gabapentin nor pregabalin induced CPP, but both compounds blocked the development of CPP to morphine and also blocked morphine's effects on dopamine release. Furthermore, pregabalin blocked the maintenance of morphine-induced CPP. It is concluded that gabapentin-like compounds, which have no intrinsic rewarding properties, may have some therapeutic use in the treatment of opioid dependence.
Andrews
N
N
Organon Laboratories Ltd, Newhouse, Lanarkshire ML1 5SH, UK. n.andrews@organon.nhe.akzonobel.nl
Loomis
S
S
Blake
R
R
Ferrigan
L
L
Singh
L
L
McKnight
A T
AT
D000085:Acetates / Q000494:pharmacology*; D000588:Amines; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003509:Cyclohexanecarboxylic Acids; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology*; D000077206:Gabapentin; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D000069583:Pregabalin; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000701:Analgesics, Opioid; D003509:Cyclohexanecarboxylic Acids; D018756:GABA Antagonists; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D004298:Dopamine