Journal of Neuroscience, Vol 9, 3400-3409, Copyright © 1989 by Society for Neuroscience
The tegmental pedunculopontine nucleus: a brain-stem output of the limbic system critical for the conditioned place preferences produced by morphine and amphetamine
A Bechara and D van der Kooy
Department of Anatomy, Faculty of Medicine, University of Toronto, Ontario, Canada.
The potent reinforcing properties of psychoactive drugs have been
attributed to the activation of motivational processes localized to the
limbic system. We investigated the role of 2 specific outputs of the
forebrain limbic system, the tegmental pedunculopontine nucleus (TPP) and
the periacqueductal gray (PAG) of the pons-midbrain, in the positive
motivational effects of morphine and amphetamine. We now report that the
TPP, but not the PAG nor other nearby regions, is a critical site in the
neural system subserving the rewarding effects of both opiates and
stimulants. Bilateral ibotenic acid lesions of the TPP blocked the positive
reinforcing effects of both morphine and amphetamine in naive rats as
measured in a conditioned place preference paradigm. However, TPP lesioned
animals were still capable of acquiring a conditioned place preference to
an environment paired with the peripheral opiate antagonist
methylnaltrexone. This suggested that TPP lesions did not cause nonspecific
deficits in the basic learning mechanisms underlying conditioned place
preferences. Furthermore, while the TPP was critical for the acquisition of
a conditioned preference to an environment paired with morphine in naive
rats, rats that had acquired a morphine conditioned place preference prior
to the lesions were capable of retaining and demonstrating these place
preferences after lesions of the TPP. This again demonstrates that TPP
lesions are producing an unconditioned deficit in motivation rather than a
deficit in learning or memory. Finally, direct comparisons of the place
preference data of individual animals with their correspondent TPP lesion
sites indicated that the most effective lesions overlapped to a greater
degree TPP perikarya with descending, rather than ascending, axons. This
suggests that motivational information generated by drug stimuli acting at
"upstream" neural structures flows in a descending direction through the
TPP region of the brain stem. These results suggest that opiates and
stimulants must ultimately activate a single brain-stem substrate in order
to have a positive motivational impact. It is hypothesized that the neural
circuits mediating the rewarding effects of drug stimuli acting at
forebrain sites exit the limbic system in the TPP region of the brain stem,
where motivation may ultimately influence or be isomorphic with the
elicitation of motor responses subserving approach and exploration.
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