Discriminative-stimulus effects of methamphetamine and morphine in rats are attenuated by cAMP-related compounds.
Animal models of drug discrimination have been used to examine the subjective effects of addictive substances. The cAMP system is a crucial downstream signaling pathway implicated in the long-lasting neuroadaptations induced by addictive drugs. We examined effects of rolipram, nefiracetam, and dopamine D2-like receptor antagonists, all of which have been reported to modulate cAMP level in vivo, on the discriminative-stimulus effects of methamphetamine (METH) and morphine in rats. All these compounds inhibited the discriminative-stimulus effects of METH, while only rolipram and nefiracetam attenuated the discriminative-stimulus effects of morphine. In addition, neither nifedipine nor neomycin, two voltage-sensitive calcium channel blockers, was found to modulate the effect of nefiracetam on METH-associated discriminative stimuli, suggesting that the inhibitory effect of nefiracetam may not involve the activation of calcium channels. These findings suggest that the cAMP signaling cascade may play a key role in the discriminative-stimulus effects of METH and morphine and may be a potential target for the development of therapeutics to counter drugs of abuse.
Yan
Yijin
Y
Department of Neuropsychopharmacology & Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Nitta
Atsumi
A
Mizuno
Tomoko
T
Nakajima
Akira
A
Yamada
Kiyofumi
K
Nabeshima
Toshitaka
T
D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002491:Central Nervous System Agents / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000378:metabolism; D004193:Discrimination Learning / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D002491:Central Nervous System Agents; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009294:Narcotics; D011760:Pyrrolidinones; C058876:nefiracetam; D008694:Methamphetamine; D009020:Morphine; D000242:Cyclic AMP; D020889:Rolipram