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Central neurotensin receptor activation produces differential behavioral responses in Fischer and Lewis rats

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Abstract

Rationale

Lewis (LEW) and Fischer (F344) rats exhibit marked differences in appetitive and consummatory responses to numerous drugs, including psychostimulants. Neurotensin (NT) produces psychostimulant-like actions, which sensitize with repeated exposure, and neuroleptic-like actions; effects that are dependent on the site of microinjection. The aim of the present experiments was to assess the behavioral sensitivity of these two strains of rats to NT receptor activation.

Methods

In expt 1, locomotor activity was assessed on alternate days following an ICV injection of NT, [d-Tyr11]neurotensin (d-NT; 18 nmol/10 μl), or vehicle (days 1, 3, 5, and 7) in independent groups of LEW and F344 rats. On day 14, locomotor activity was assessed in all rats following an injection of d-amphetamine (1 mg/kg, IP). In expt 2, activity was assessed following injection into the ventral tegmental area of NT, or d-NT, (2.5 μg/hemisphere) or into the nucleus accumbens (2.5 and 5.0 μg/hemisphere).

Results

Repeated ICV injections of NT, or d-NT, produced differential behavioral effects in the two strains of rats on days 1–7; activity was initially suppressed in LEW, but less so in F344 rats, following NT. In F344, but not in LEW rats, d-NT produced a significant increase in activity. Neurotensin and d-NT sensitized LEW rats to amphetamine-induced ambulatory and non-ambulatory activity. Except for vertical activity, this effect was weaker or in the opposite direction in F344 rats. When injected into the ventral tegmental area, NT produced an increase in locomotor activity in both strains, an effect that was greater in F344 than LEW rats with d-NT. In the nucleus accumbens, NT marginally decreased activity in both strains, while d-NT produced a significant increase in F344 but not in LEW rats.

Conclusions

These results provide empirical evidence that endogenous NT neurotransmission within limbic circuitry differs in F344 and LEW rats.

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Acknowledgements

This study was supported by a grant from the Canadian Institutes of Health Research (CIHR) to PPR and a Post-Doctoral Research Fellowship to P.B. from the CIHR and The Schizophrenia Society of Canada.

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Authors and Affiliations

  1. Département de Psychiatrie, Université de Montréal, Montréal, Québec, Canada H1N 3V2

    Pat Bauco & Pierre-Paul Rompré

  2. Centre de Recherche Fernand-Seguin, Hôpital Louis-H. Lafontaine, 7331 rue Hochelaga, Montréal, Québec, Canada H1N 3V2

    Pat Bauco & Pierre-Paul Rompré

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Correspondence to Pat Bauco.

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Bauco, P., Rompré, PP. Central neurotensin receptor activation produces differential behavioral responses in Fischer and Lewis rats. Psychopharmacology 168, 253–261 (2003). https://doi.org/10.1007/s00213-003-1436-8

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