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

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-Tyr(11)]neurotensin ( d-NT; 18 nmol/10 microl), 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 microg/hemisphere) or into the nucleus accumbens (2.5 and 5.0 microg/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.