Sd. Glick et al., NEUROCHEMICAL PREDISPOSITION TO SELF-ADMINISTER COCAINE IN RATS - INDIVIDUAL-DIFFERENCES IN DOPAMINE AND ITS METABOLITES, Brain research, 653(1-2), 1994, pp. 148-154
Using in vivo microdialysis, this study attempted to determine whether
a neurochemical predisposition to self-administer cocaine could be id
entified. Estimated extracellular levels of dopamine and its metabolit
es were measured bilaterally in the mesocorticolimbic and nigrostriata
l systems of naive rats that were subsequently trained to self-adminis
ter cocaine intravenously. There were several significant relationship
s between dopamine and dopamine metabolite (3,4-dihydroxyphenylacetic
acid and homovanillic acid) levels and rates of cocaine self-administr
ation during both acquisition and asymptotic phases of testing. Dopami
ne levels in the nucleus accumbens were non-monotonically related to r
ates of self-administration during both phases: low to moderate dopami
ne levels were positively correlated with self-administration rates wh
ereas moderate to high dopamine levels were negative correlated with s
elf-administration rates. Dopamine, DOPAC (3,4-dihydroxyphenylacetic a
cid) and HVA (homovanillic acid) levels in the striatum were inversely
correlated with self-administration rates during the acquisition phas
e. DOPAC and HVA levels in the left and right sides of the medial pref
rontal cortex were positively and negatively correlated, respectively,
with self-administration rates during the asymptotic phase; left/righ
t asymmetries in cortical metabolite levels were also correlated with
asymptotic rates. There were no significant relationships between any
neurochemical indices and rates of bar-pressing for water. These resul
ts suggest that the normal variability in drug seeking behavior is at
least in part attributable to individual differences in the activity o
f brain dopamine systems. Furthermore, different mechanisms appear to
be responsible for the acquisition and maintenance phases of cocaine s
elf-administration: dopamine release in the nucleus accumbens appears
to be a critical component of both mechanisms, with an optimal level o
f dopamine appearing to be a major predisposing factor: dopamine relea
se in the striatum appears to modulate acquisition; and there appears
to be a left-right lateralized influence of the medial prefrontal cort
ex on maintenance. Although previous data have indicated that dopamine
rgic activity in the same brain regions also predisposes rats to self-
administer morphine, the precise determinants of morphine and cocaine
self-administration appear to be substantially different in terms of h
ow these dopaminergic brain regions act and interact.