Manipulations of mu-opioid and nicotinic cholinergic receptors in the pontine tegmental region alter cocaine self-administration in rats.
BACKGROUND
The pedunculopontine tegmental nucleus (PPTg) has been implicated in drug reward, particularly in the development of dependence. However, little is known of the receptor systems within this nucleus which might be involved. Furthermore, some research suggests that the PPTg may also be part of the neuronal circuitry involved in established drug-taking behavior.


OBJECTIVE
The objective of these experiments was to examine the role of mu-opioid and nicotinic cholinergic mechanisms in the PPTg in cocaine self-administration.


METHODS
Microinfusions of mu-opioid and nicotinic receptor selective compounds were made into the PPTg of rats trained to self-administer cocaine intravenously, in the vicinity of cholinergic cells which are known 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 microg, produced a dose-related reduction in the number of cocaine infusions obtained during the 1-h self-administration sessions. The mu-selective antagonist CTOP (0-2 microg) and nicotine (0-10 microg) did not produce significant changes in cocaine self-administration. Microinfusions of the nicotinic antagonist dihydro-beta-erythroidine (0-30 microg) produced a small but significant increase in cocaine-maintained responding.


CONCLUSIONS
These data show that mu-opioid mechanisms in the PPTg can influence cocaine 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 (as shown by previous research).
Corrigall
W A
WA
Biobehavioural Research Department, Centre for Addiction and Mental Health, ARF Division, 33 Russell Street, Toronto, Ontario, Canada, M5S 2S1. bcorriga@arf.org
Coen
K M
KM
Adamson
K L
KL
Chow
B L
BL
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D011149:Pons / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D011978:Receptors, Nicotinic / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D012646:Self Administration; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology
D004745:Enkephalins; D011978:Receptors, Nicotinic; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D003042:Cocaine