Attempts to determine the neural circuitry where addictive drugs act to establish drug-seeking habits are aided by demonstration of drug self-administration directly into local brain regions. In the past year we have discovered that rats will learn to lever-press for injections of the cholinergic agent carbachol and the recently isolated endogenous ligand for the mu opiate receptor, endomorphin-1, directly into the ventral tegmental area, where the mesolimbic dopamine system originates. In each case we find evidence for differential effectiveness in the rostral and caudal portions of the ventral tegmental area. Endomorphin-1 was not self-administered into nucleus accumbens, where the mesolimbic dopamine system terminates. Animals would respond for neither substance when injected dorsal to the ventral tegmental area, ruling out diffusion up the cannula shaft to a distal site of action. These findings implicate projections from the pedunculopontine tegmental or dorsolateral tegmental pontine nuclei and from the arcuate nucleus in the neural network within which addictive drugs establish compulsive drug self-administration habits.
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