Effects of N-Methyl-D-Aspartate receptor blockade on cross-sensitization between D-Tyr11 neurotensin and amphetamine

Blockade of neurotensin (NT) receptors with SR-48692 prevents the development of sensitization to the locomotor activating effects of amphetamine (AMPH). In addition, repeated icv injections of NT or of its analog, D-Tyr 11 NT, sensitize animals to the locomotor activating effects of AMPH. Recent evidence indicates a role for glutamate (GLU) in the development of sensitization to psychostimulant drugs inasmuch as co-administration of GLU antagonists prevents induction of AMPH and cocaine sensitization. The present study was aimed at testing the hypothesis that endogenous glutamatergic systems also play a role in the induction of cross-sensitization between NT and AMPH. Experiments were performed on male rats implanted with a guide cannula above the left lateral ventricle. During the induction phase, locomotor activity was measured on four occasions every second day for two hours after an icv injection of 18nmol/10ol of D-Tyr 11 NT, or saline, preceded 30 min before by a systemic injection of CPP, [(+/-)-3-(2-carboxypiperazine-4-yl)-propanephosphonic] (4 mg/kg), a GLU antagonist, or its vehicle. One week after the induction phase, locomotor activity to a single injection of AMPH (0.75mg/kg) was measured in all rats (sensitization test). Results show that AMPH induced greater ambulatory activity in animals pretreated with D-Tyr 11 NT alone, a sensitization effect that was attenuated by CPP given during the induction phase. These results suggest that GLU may play a role in the development of cross-sensitization between D-Tyr 11 NT and AMPH