Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo.
Differential pulse voltammetry with carbon fibre electrodes was used to study the effect of central administration of neurotensin on the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum in anaesthetised rats. Intracerebroventricular injection of neurotensin (10 micrograms) increased the peak height for DOPAC 20 min after administration in the nucleus accumbens but only after 40 min in the striatum. The maximum increase was similar in both regions, with 30% and 27% above the pre-injection basal level, respectively. Neurotensin (1 micrograms) however increased the extracellular level of DOPAC in the nucleus accumbens alone. Neurotensin (0.1, 1.0 and 3.0 micrograms/0.5 microliter), injected into the ventral tegmental area, induced a potent and long-lasting elevation of the peak height for DOPAC in the nucleus accumbens, while the same doses in the substantia nigra produced effects on the metabolism of dopamine in the striatum of smaller amplitude and shorter duration. The maximum effect of each dose was about 2.5 times greater in the mesolimbic, compared to the nigrostriatal system. Amphetamine (2 mg/kg, s.c.) decreased the extracellular level of DOPAC with a similar magnitude, both in the nucleus accumbens (52%) and the striatum (47%). Intracerebroventricular administration of neurotensin (1 micrograms), 5 min after amphetamine, did not alter the effect of amphetamine on the extracellular level of DOPAC either in the nucleus accumbens or the striatum. However, neurotensin (10 micrograms) partially reversed the effect of amphetamine in the nucleus accumbens and had a similar but smaller and delayed effect in the striatum. The results from the present study, together with previous neurobehavioural studies, suggest that neurotensin has a relatively selective action on the mesolimbic dopaminergic system in the rat.
Rivest
R
R
Department of Psychiatry, Medical School, University of Sherbrooke, Quebec, Canada.
Jolicoeur
F B
FB
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 / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D007276:Injections, Intraventricular; D007700:Kinetics; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D015102:3,4-Dihydroxyphenylacetic Acid; D009496:Neurotensin; D004298:Dopamine