Wa. Corrigall et al., Manipulations of mu-opioid and nicotinic cholinergic receptors in the pontine tegmental region alter cocaine self-administration in rats, PSYCHOPHAR, 145(4), 1999, pp. 412-417
Rationale: The pedunculopontine tegmental nucleus (PPTg) has been implicate
d in drug reward, particularly in the development of dependence. However, l
ittle is known of the receptor systems within this nucleus which might be i
nvolved. Furthermore, some research suggests that the PPTg may also be part
of the neuronal circuitry involved in established drug-taking behavior. Ob
jective: The objective of these experiments was to examine the role of mu-o
pioid and nicotinic cholinergic mechanisms in the PPTg in cocaine self-admi
nistration. Methods: Microinfusions of mu-opioid and nicotinic receptor sel
ective compounds were made into the PPTg of rats trained to self-administer
cocaine intravenously, in the vicinity of cholinergic cells which are know
n to project to the midbrain dopamine neurons of the ventral tegmental area
(VTA). Results: The mu-opioid selective agonist DAMGO, tested at doses of
0, 0.05 and 0.5 mu g, produced a dose-related reduction in the number of co
caine infusions obtained during the 1-h self-administration sessions. The m
u-selective antagonist CTOP (0-2 mu g) and nicotine (0-10 mu g) did not pro
duce significant changes in cocaine self-administration, Microinfusions of
the nicotinic antagonist dihydro-beta-erythroidine (0-30 mu g) produced a s
mall but significant increase in cocaine-maintained responding. Conclusions
: These data show that mu-opioid mechanisms in the PPTg call influence coca
ine self-administration markedly. Moreover, the data demonstrate that PPTg
circuitry can influence drug reward in already-established drug-reinforced
behavior, as well as during the development of dependence las shown by prev
ious research).