Manipulations of mu-opioid and nicotinic cholinergic receptors in the pontine tegmental region alter cocaine self-administration in rats

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).