title: Lesions of the tegmental pedunculopontine nucleus: effects on the locomotor activity induced by morphine and amphetamine.
abstract: One of the important questions in the neurobiology of motivation asks how the incentive impact of stimuli acting on the limbic system of the forebrain are ultimately translated into action and approach behavior. Bilateral ibotenic acid lesions of the tegmental pedunculopontine nucleus (TPP) (a brainstem output of the limbic system that receives neuronal input from limbic forebrain and midbrain sites identified as primary sites for psychoactive drug reward) have been shown previously to block the acquisition, but not the retention, of morphine and amphetamine conditioned place preferences in formerly drug-naive rats. These results suggest a deficit in the processing of the unconditioned rewarding effects of these drugs. The TPP projects to widespread parts of the brain and spinal cord involved in various somatomotor responses. Thus, we investigated the role of the TPP in morphine- and amphetamine-induced locomotion as assessed in an open field. We report that TPP lesions blocked the locomotor excitation, as well as the conditioned hyperactivity, produced by amphetamine. TPP lesions also blocked the conditioned increase in locomotion, but not the catalepsy, produced by morphine. TPP lesions were behaviorally specific in that the analgesic properties of morphine in a tail-flick test were not attenuated, nor did the lesions affect the locomotion induced by naloxone-precipitated withdrawal in morphine-dependent animals. We suggest that the neural circuits mediating the acute rewarding effects of drug stimuli acting at forebrain sites exit the limbic system in the TPP region of the brainstem, where motivation gains access to (or is isomorphic with) motor systems that initiate approach and exploration.
authors.affiliation: Department of Anatomy, University of Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bechara
authors.forename: D
authors.initials: D
authors.lastname: van der Kooy
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D011149:Pons / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013681:Tegmentum Mesencephali / Q000033:anatomy & histology / Q000502:physiology*
chemical_list: D009270:Naloxone; D009020:Morphine; D000661:Amphetamine