In vivo neurochemical and behavioural effects of intracerebrally administered neurotensin and D-Trp11-neurotensin on mesolimbic and nigrostriatal dopaminergic function in the rat.
The effects of intracerebral application of neurotensin on the behavioural responses to peripheral dopamine agonist administration to rats, and on the levels of DOPAC voltammetrically determined in the striatum and nucleus accumbens of the anaesthetized rat have been examined. Bilateral application of neurotensin to the nucleus accumbens, like the neuroleptic haloperidol, inhibited the hyperactivity response to the dopamine agonist, n,N-propylnorapomorphine, but, unlike haloperidol, its bilateral intrastriatal application failed to reduce the degree of stereotyped behaviour induced by peripheral apomorphine injection. In the halothane-anaesthetized rat, neurotensin, when applied to the ventral tegmental area, stimulated DOPAC production in the ipsilateral nucleus accumbens, while its application to the substantia nigra did not affect striatal DOPAC levels significantly. Following its intracerebroventricular injection, however, DOPAC levels were considerably enhanced in both regions. The 11-D-tryptophan-substituted analogue of neurotensin potently mimicked the effects of the peptide itself in all studies. The findings of these investigations further confirm in vivo that the functional antagonism of dopamine by neurotensin is selective for the mesolimbic system, and that the effects of neurotensin can be correlated with reports on the regional distribution of its high-affinity binding sites in the rat brain.
Ford
A P
AP
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, U.K.
Marsden
C A
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007267:Injections; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009496:Neurotensin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D015102:3,4-Dihydroxyphenylacetic Acid; D009496:Neurotensin; C024309:neurotensin, Trp(11)-; D006220:Haloperidol; D004298:Dopamine