Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor

Autor: Maja Franceschi, Madina R. Gerasimov, Wynne K. Schiffer, Onarae V. Rice, Stephen L. Dewey, Nora D. Volkow
Rok vydání: 2000
Předmět:
Zdroj: Synapse. 38:432-437
ISSN: 1098-2396
0887-4476
DOI: 10.1002/1098-2396(20001215)38:4<432::aid-syn8>3.0.co;2-q
Popis: There is a greater prevalence of cigarette smoking among cocaine- dependent individuals and hyperactive children treated with stimulants (e.g., methyl- phenidate, MP). However, little is known about the neurochemical basis of the interac- tion between nicotine and cocaine or MP. It is thought that the reinforcing effects of cocaine and MP are due partly to increases in synaptic DA in the nucleus accumbens (NAc). These measurable increases are secondary to the blockade of the DA transporter. In contrast, nicotine stimulates acetylcholine receptors located presynaptically on do- paminergic projections from the ventral tegmental area (VTA) to the NAc and increases DA transmission. Here we investigate the effects of nicotine on NAc DA in animals simultaneously injected with cocaine or MP. Coadministration of nicotine (0.4 mg/kg s.c.) and cocaine (10 mg/kg i.p.) or MP (5 mg/kg i.p.) increased the extracellular NAc DA levels in an additive manner, while coadministration of nicotine (0.4 mg/kg s.c.) and a higher dose of cocaine (20 mg/kg) or MP (10 mg/kg) clearly produced a synergistic elevation in NAc DA. These findings suggest that the degree of DA transporter (DAT) occupancy contributes to the synergistic interaction between nicotine and cocaine or MP. Synapse 38:432- 437, 2000. © 2000 Wiley-Liss, Inc.
Databáze: OpenAIRE
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