Role of context in neurotensin-induced sensitization to the locomotor stimulant effect of amphetamine

• Acute neurotensin attenuates spontaneous locomotion.
• Neurotensin sensitizes to amphetamine-induced locomotor behavior.
• The cross-sensitization effect of neurotensin is context-dependent and independent.

Previous studies have shown that repeated central injections of neurotensin, or its active analog, d-Tyr[11]neurotensin, sensitize to the locomotor stimulant effect of amphetamine. The development of sensitization to amphetamine can be modulated by contextual stimuli associated with the drug and as a consequence the expression of sensitization becomes context-dependent. The present study was thus aimed at determining whether the induction of amphetamine sensitization by neurotensin is modulated by the context in which neurotensin is administered. Different groups of adult male Long Evans rats were injected on four occasions with d-Tyr[11]neurotensin (18 nmol/10 μl; i.c.v.) in the locomotor activity cages (paired group) or in their home cage (unpaired group); control group received vehicle injection in both environments. One week after the last central injection, the locomotor response to a single dose of amphetamine (0.75 mg/kg; i.p.) was measured in all the rats. Results show that amphetamine induced higher ambulatory, non-ambulatory and vertical activity in the paired group than in the control group confirming the sensitization effect. The paired group also displayed significant higher ambulatory activity than those in the unpaired group, confirming that the expression of sensitization was context-dependent. This context-dependency was not found however for amphetamine-induced non-ambulatory and vertical activity suggesting that neurotensin can induce both a context-dependent and context-independent sensitization.