Neurotensin modulation of spontaneous EPSCs in the nucleus accumbens of Lewis and Fischer 344 rats.
Fischer 344 (F344) and Lewis (LEW) rats are inbred strains that are differentially sensitive to drugs of abuse and that respond differently to the endogenous neuropeptide neurotensin (NT). To understand the mechanisms involved we used whole cell patch clamp recording technique to study the effects of an equimolar concentration of NT and its active analog, d-Tyr[11]neurotensin (d-NT), on the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in nucleus accumbens medium spiny (MS) neurons in brain slices. NT and d-NT produced an increase in the amplitude but not in the frequency of sEPSCs in all neurons tested in both F344 and LEW rats. In LEW rats, NT and d-NT produced an increase in sEPSCs of the same magnitude. In contrast, in F344 rats, d-NT produced an increase in sEPSCs that was 2.4 times larger than that of NT. Moreover, the effect of d-NT in F344 rats was also significantly larger than that measured in LEW rats whereas NT produced an effect of the same magnitude in both strains. These results demonstrate that MS neurons in F344 rats are more responsive to the activation of NT receptors sensitive to d-NT than LEW animals. This finding parallels previous behavioral data and provides additional evidence that the NT circuitry differs in the two strains, in a brain region known to play a key role in the rewarding effects of drugs of abuse.
Centre de Recherche Fernand-Seguin, University of Montreal, 7331 Hochelaga Street, Montreal, Quebec, Canada H1N 3V2.
Shou-Wei
SW
Yang
Pierre-Paul
PP
Rompré
Richard A
RA
Warren
D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009496:Neurotensin / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
D009496:Neurotensin