Positive reinforcing properties of nicotine and the psychostimulants have been attributed
to elevated dopamine release in the basal ganglia. It is well known that the specific
binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced
by cocaine and amphetamines, revealing increased competition between endogenous dopamine
and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride
binding to nicotine-induced dopamine release is less well documented. In order to
provide the basis for mapping effects of nicotine, we first optimized reference tissue
methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs
(n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using
[(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of
nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition
for calculating the binding of radioligands when using a reference tissue to estimate
the free ligand concentration. The methods of Logan and of Lammertsma were compared
using the cerebellum or the occipital cortex as reference tissues for calculating
the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method
used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric,
with highest binding in the left caudate and right putamen. Test-retest estimates
of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine
reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral
striatum, but this effect did not persist after correction for multiple comparisons.
The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral
striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and
caudally into the caudate and putamen. Evidently, nicotine challenge enhances the
competition between endogenous dopamine for [(11)C]raclopride binding sites with a
complex temporal and spacial pattern in pig brain, initially presenting in the left
ventral striatum.