Wa. Corrigall et al., The mu opioid agonist DAMGO alters the intravenous self-administration of cocaine in rats: mechanisms in the ventral tegmental area, PSYCHOPHAR, 141(4), 1999, pp. 428-435
Microinfusions of the opioid subtype-selective agonist DAMGO and antagonist
CTOP into the ventral tegmental area (VTA) were used to examine the role o
f mu opioid receptors in this area of the mesolimbic dopamine system in reg
ulating cocaine reinforcement. Long-Evans rats were trained to self-adminis
ter cocaine intravenously and prepared with intracranial cannulae directed
to the VTA, At doses of cocaine on the descending limb of the cocaine dose-
response curve, the mu-selective agonist DAMGO produced a dose-related decr
ease in cocaine self-administration when delivered by microinfusion into th
e VTA. At a dose of cocaine on the ascending limb of the self-administratio
n dose-response curve, DAMGO microinfusions produced an increase in respond
ing for the drug, The mu-selective antagonist CTOP produced small effects o
n cocaine self-administration. A kappa-selective agonist and antagonist (U5
0,488 and norbinaltorphimine, respectively) produced either no effects or s
mall effects that did not show consistent trends with dose, These experimen
ts suggest that the mu agonist DAMGO is able to shift the dose-response cur
ve for cocaine self-administration to the left. This effect appears to be s
pecific for mu as compared to kappa agonists. These data are consistent wit
h the known differential distribution of opioid receptor subtypes within th
e VTA, and with the effects of opioid compounds in the VTA on dopa mine rel
ease in the mesolimbic synaptic field. The data show that a mu opioid mecha
nism in the somatodendritic region can alter reinforcement processes for co
caine, which acts predominantly at the terminal field of dopamine cells.