Synergistic interactions between nicotine and cocaine or methylphenidate depend on the dose of dopamine transporter inhibitor.
There is a greater prevalence of cigarette smoking among cocaine-dependent individuals and hyperactive children treated with stimulants (e.g., methylphenidate, MP). However, little is known about the neurochemical basis of the interaction 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 dopaminergic 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.
Gerasimov
M R
MR
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA. madina@bnl.gov
Franceschi
M
M
Volkow
N D
ND
Rice
O
O
Schiffer
W K
WK
Dewey
S L
SL
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008774:Methylphenidate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; C493216:Slc6a3 protein, rat; D008774:Methylphenidate; D009538:Nicotine; D003042:Cocaine; D004298:Dopamine