Behavioural effects of substance P through dopaminergic pathways in the brain.
Some of the highest concentrations of substance P in forebrain are found in areas where dopaminergic neurons arise or terminate. In the rat, native substance P has been injected directly into brain areas where interactions between substance P and dopamine are suspected. In the ventral tegmental area (A10 dopamine neurons), bilateral infusions of substance P induce locomotor activity and exploration. It is concluded that substance P activates A10 dopamine neurons innervating the limbic system because (i) the behavioural effects resemble those seen after systemic treatment with low doses of d-amphetamine, a drug response known to depend on the integrity of the A10 dopamine neurons; (ii) lesions to the A10 dopamine neurons abolish the behavioural response to intracerebrally infused substance P; and (iii) dopamine antagonist drugs abolish the response to substance P. In parallel experiments substance P was injected into the origins of the nigrostriatal (A9 dopamine neurons) system and found to produce stereotyped behaviour. Substance P analogues protected from enzymic degradation have been studied in these model systems. The prolongation of the behavioural effects is correlated with the presence of undegraded substance P in the ventral tegmental area. Unrelated behavioural responses are also observed, which appear not to be mediated by dopamine neurons, and probably reflect the spread of stable substance P from the ventral tegmental area to other brain sites.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004027:Diencephalon / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004355:Drug Stability; D010450:Endopeptidases / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008032:Limbic System / Q000502:physiology; D008666:Metalloendopeptidases; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D016627:Oxidopamine; D010446:Peptide Fragments; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D013687:Telencephalon / Q000502:physiology
D006892:Hydroxydopamines; D010446:Peptide Fragments; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D016627:Oxidopamine; D010450:Endopeptidases; D008666:Metalloendopeptidases; C029610:substance P degrading enzyme; D011761:Pyrrolidonecarboxylic Acid; D003913:Dextroamphetamine; D004298:Dopamine