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Psychopharmacology

, Volume 113, Issue 3–4, pp 378–380 | Cite as

Effects of the calcium antagonist isradipine on cocaine intravenous self-administration in rats

  • M. Cristina Martellotta
  • Alexander Kuzmin
  • Pierandrea Muglia
  • Gian Luigi Gessa
  • Walter Fratta
Original Investigations

Abstract

The effect of isradipine, a dihydropyridine calcium antagonist, on cocaine intravenous self-administration in rats was investigated. Administration of (±)isradipine (1.25–5 mg/kg SC) 2 h before the cocaine self-administration session induced a significant and dose-dependent increase in the number of coacine injections with respect to basal values. This effect was sterospecific, with the (+) form of isradipine being active, while the (−) stereoisomer was ineffective. These results suggest that isradipine antagonizes the rewarding properties of cocaine, possibly by inhibiting those dopaminergic systems related to reward mechanisms. These results further indicate a possible use of isradipine, or structurally similar compounds, in the treatment of cocaine related disorders.

Key words

Cocaine Self-administration Calcium antagonists Isradipine Dopamine Rat 

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References

  1. Calcagnetti DJ, Schechter MD (1992) Attenuation of drinking sweetened water following calcium channel blockade. Brain Res Bull 28:967–973CrossRefPubMedGoogle Scholar
  2. Carboni E, Imperato A, Perezzani L, Di Chiara G (1989) Amphetamine, cocaine, phencyclidine and nomiphensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience 28:653–661CrossRefPubMedGoogle Scholar
  3. Chaudieu I, Alonso R, Mount H, Quirion R, Boksa P (1992) Effects of L- and N-type Ca2+ channel antagonists on excitatory amino acid-evoked dopamine release. Eur J Pharmacol 220:203–209CrossRefPubMedGoogle Scholar
  4. Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increased synaptic dopamine concentration in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5278PubMedGoogle Scholar
  5. Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: mediation by separate neural system. Psychopharmacology 78:204–209CrossRefGoogle Scholar
  6. Ferry DR, Glossmann H (1982) Identification of putative calcium channel in skeletal muscle microsomes. FEBS Lett 148:331–337CrossRefPubMedGoogle Scholar
  7. Fratta W, Kuzmin A, Martellotta MC, Gessa GL (1991) The calcium antagonist isradipine inhibits cocaine and morphine reinforcing properties in rats. Soc Neurosci Abstr 17:887Google Scholar
  8. Goll A, Ferry DR, Glossmann H (1983) Target size analysis of skeletal muscle Ca2+ channels. FEBS Lett 157:63–69CrossRefPubMedGoogle Scholar
  9. Griffiths RR, Bigelow GE, Henningfield JE (1980) Similarities in animal and human drug taking behavior. In: Mello NK (ed) Advances in substance abuse, vol. 1. JAI Press, Greenwich Connecticut, pp 1–90Google Scholar
  10. Johanson CE, Fischman MW (1989) The pharmacology of cocaine related to its abuse. Pharmacol Rev 41:3–52PubMedGoogle Scholar
  11. Kato T, Otsu Y, Furune Y, Yamamoto T (1992) Different effects of L-, N- and T-type calcium channel blockers on striatal dopamine release measured by microdialysis in freely moving rats. Neurochem Int 21:99–107CrossRefPubMedGoogle Scholar
  12. Koob GF (1992) Drug of abuse: anatomy, pharmacology and function of reward pathways. TIPS 13:177–184PubMedGoogle Scholar
  13. Kuzmin A, Zvartau E, Gessa GL, Martellotta MC, Fratta W (1992) Calcium antagonists isradipine and nimodipine suppress cocaine and morphine intravenous self-administration in drugnaive mice. Pharmacol Biochem Behav 41:497–500Google Scholar
  14. Lee HR, Roeske WR, Yamamura HI (1984) High affinity specific [3H](+)PN 200–110 binding to dihydropyridine receptors associated with calcium channels in rat cerebral cortex and heart. Life Sci 35:721–732CrossRefPubMedGoogle Scholar
  15. Le Moal M, Simon H (1991) Mesocorticolimbic dopaminergic network: functional and regulatory roles. Physiol Rev 71:155–234PubMedGoogle Scholar
  16. Pani L, Carboni S, Kuzmin A, Gessa GL, Rossetti ZL (1990a) Nimodipine inhibits cocaine-induced dopamine release and motor stimulation. Eur J Pharmacol 176:245–246CrossRefPubMedGoogle Scholar
  17. Pani L, Kuzmin A, Diana M, De Montis G, Gessa GL, Rossetti ZL (1990b) Calcium antagonists differ in modifyng cocaine effects in the CNS. Eur J Pharmacol 190:217–221CrossRefPubMedGoogle Scholar
  18. Pani L, Kuzmin A, Martellotta MC, Gessa GL, Fratta W (1991) The calcium antagonist PN 200–110 inhibits the reinforcing properties of cocaine. Brain Res Bull 26:445–447CrossRefPubMedGoogle Scholar
  19. Supavilai P, Karobath M (1984) The interaction of [3H]PY 108–068 and of [3H]PN 200–110 with calcium channel binding sites in rat brain. J Neural Transm 60:149–167CrossRefPubMedGoogle Scholar
  20. Wise RW (1987) The role of reward pathways in the development of drug dependence. Pharmacol Ther 35:227–263CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • M. Cristina Martellotta
    • 1
  • Alexander Kuzmin
    • 2
  • Pierandrea Muglia
    • 1
  • Gian Luigi Gessa
    • 1
  • Walter Fratta
    • 1
  1. 1.B.B. Brodie Department of NeuroscienceUniversity of CagliariCagliariItaly
  2. 2.Department of PharmacologyPavlov Medical InstituteSt. PetersburgRussia

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