Summary
Methamphetamine (MA) is well known as a potent CNS stimulant, which produces strong rewarding and behavioral sensitization after repeated administration. In the present study, we investigated whether co-administration of dextromethorphan (DM) with MA could suppress these effects induced by acute and chronic MA treatment. The conditioned place preference (CPP) test was used to examine the rewarding/drug seeking effects and locomotor and stereotypic activities were measured to investigate behavioral sensitization induced by chronic MA. Our results revealed that co-administration of DM (20 mg/kg, ip) with MA (2 mg/kg, ip) almost completely abolished the MA-induced CPP and behavioral sensitization. Furthermore, both of the acute and chronic MA could result in an increase of dopamine (DA) turnover rate in the NAc and mPFC. The acute effects of MA on DA turnover rate could be attenuated by the co-administration of DM in both regions. The chronic effect of MA on DA turnover rate in the mPFC was also attenuated by the co-administration of DM. These results suggest that the effect of DM on blocking MA-induced rewarding and behavioral sensitization may be related to its effect on inhibiting the activity of DA neurons projected to mPFC and/or NAc.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Hoffman D.C. (1989) The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Res Bull. 23:373–387
Swerdlow N.R., Vaccarino F.J., Amalric M., Koob G.F. (1986) The neural substrates for the motor-activating properties of psychostimulants: a review of recent findings. Pharmacol. Biochem. Behav. 25:233–248
Simon H., Scatton B., Moal M.L. (1980) Dopaminergic A10 neurones are involved in cognitive functions. Nature 286:150–151
Kalivas P.W., Stewart J. (1991) Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activity. Brain Res. Brain Res. Rev. 16:223–244
Strakowski S.M., Sax K.W. (1998) Progressive behavioral response to repeated d-amphetamine challenge: further evidence for sensitization in humans. Biol. Psych. 44:1171–1177
Wolf M.E. (1998) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog. Neurobiol. 54:679–720
Tiseo P.J., Cheng J., Pasternak G.W., Inturrisi C.E. (1994) Modulation of morphine tolerance by the competitive N-methyl-D-aspartate receptor antagonist LY274614: assessment of opioid receptor changes. J Pharmacol Exp Ther. 268:195–201
Trujillo K.A., Akil H. (1995) Excitatory amino acids and drugs of abuse: a role for N-methyl-d-aspartate receptors in drug tolerance, sensitization and physical dependence. Drug Alcohol Depend. 38:139–154
Tokuyama S., Wakabayashi H., Ho I.K. (1996) Direct evidence for a role of glutamate in the expression of the opioid withdrawal syndrome. Eur. J. Pharmacol. 295:123–129
Bem J.L., Peck R. (1992) Dextromethorphan. An overview of safety issues. Drug Saf. 7:190–199
Church J., Sawyer D., McLarnon J.G. (1994) Interactions of dextromethorphan with the N-methyl-d-aspartate receptor-channel complex: single channel recordings. Brain Res. 666:189–194
Farzin D. (1999) Modification of naloxone-induced withdrawal signs by dextromethorphan in morphine-dependent mice. Eur. J. Pharmacol. 377:35–42
Mao J., Price D.D., Caruso F.S., Mayer D.J. (1996) Oral administration of dextromethorphan prevents the development of morphine tolerance and dependence in rats. Pain 67:361–368
Huang E.Y., Liu T.C., Tao P.L. (2003) Co-administration of dextromethorphan with morphine attenuates morphine rewarding effect and related dopamine releases at the nucleus accumbens. Naunyn Schmiedebergs Arch. Pharmacol. 368: 386–392
Ranaldi R., Munn E., Neklesa T., Wise R.A. (2000) Morphine and amphetamine sensitization in rats demonstrated under moderate- and high-dose NMDA receptor blockade with MK-801 (dizocilpine). Psychopharmacology (Berl) 151:192–201
Tzschentke T.M. (1998) Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues. Prog. Neurobiol. 56:613–672
Joyce E.M., Iversen S.D. (1979) The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci. Lett. 14:207–212
Vezina P., Stewart J. (1984) Conditioning and place-specific sensitization of increases in activity induced by morphine in the VTA. Pharmacol. Biochem. Behav. 20:925–934
Kelly P.H., Seviour P.W., Iversen S.D. (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 94:507–522
Kim H.S., Jang C.G. (1997) MK-801 inhibits methamphetamine-induced conditioned place preference and behavioral sensitization to apomorphine in mice. Brain Res. Bull. 44:221–227
Jhoo W.K., Shin E.J., Lee Y.H., Cheon M.A., Oh K.W., Kang S.Y., Lee C., Yi B.C., Kim H.C. (2000) Dual effects of dextromethorphan on cocaine-induced conditioned place preference in mice. Neurosci. Lett. 288:76–80
Itzhak Y., Martin J.L. (2000) Effect of riluzole and gabapentin on cocaine- and methamphetamine-induced behavioral sensitization in mice. Psychopharmacology (Berl) 151:226–233
Ujike H., Tsuchida H., Kanzaki A., Akiyama K., Otsuki S. (1992) Competitive and non-competitive N-methyl-d-aspartate antagonists fail to prevent the induction of methamphetamine-induced sensitization. Life Sci. 50:1673–1681
Li Y., Vartanian A.J., White F.J., Xue C.J., Wolf M.E. (1997) Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine. Psychopharmacology (Berl) 134:266–276
Segal D.S., Kuczenski R., Florin S.M. (1995) Does dizocilpine (MK-801) selectively block the enhanced responsiveness to repeated amphetamine administration? Behav. Neurosci. 109:532–546
Acknowledgment
This study was supported by the grants from National Science Council (NSC 93–2320-B-016–033), Taipei, Taiwan, Republic of China.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yang, PP., Huang, E.YK., Yeh, GC. et al. Co-administration of dextromethorphan with methamphetamine attenuates methamphetamine-induced rewarding and behavioral sensitization. J Biomed Sci 13, 695–702 (2006). https://doi.org/10.1007/s11373-006-9096-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11373-006-9096-4