TY - JOUR
T1 - Discriminative-stimulus effects of methamphetamine and morphine in rats are attenuated by cAMP-related compounds
AU - Yan, Yijin
AU - Nitta, Atsumi
AU - Mizuno, Tomoko
AU - Nakajima, Akira
AU - Yamada, Kiyofumi
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This study was supported in part by a Grant-in-Aid for Scientific Research and Special Coordination Funds for Promoting Science and Technology, Target-Oriented Brain Science Research Program, from the Ministry of Education, Culture, Sports, Science and Technology of Japan; by a Grant-in-Aid for Health Science Research on Regulatory Science of Pharmaceuticals and Medical Devices, and Dementia and Fracture from the Ministry of Health, Labor and Welfare of Japan; by a Grant-in-Aid for Scientific Research (B) and Young Scientists (A); by the 21st Century Center of Excellence Program “Integrated Molecular Medicine for Neuronal and Neoplastic Disorders” from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and in part by Uehara Memorial Foundation Research Fellows.
PY - 2006/10/2
Y1 - 2006/10/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2006.05.029
DO - 10.1016/j.bbr.2006.05.029
M3 - Article
C2 - 16857277
AN - SCOPUS:33749985646
VL - 173
SP - 39
EP - 46
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -