Vanessa Lopak1, Suzanne Erb. 1. Centre for the Neurobiology of Stress, Departments of Life Science and Psychology, University of Toronto at Scarborough, Toronto, Ontario, M1A 1C4, Canada.
Abstract
RATIONALE: Neurotensin (NT) has been implicated in some of the behavioral effects of psychostimulants. Thus, there is reason to think that NT may play a role in the reinstatement of cocaine seeking, and that it may do so via an interaction with dopamine (DA). OBJECTIVES: To assess (1) whether NT and an NT analog, D-TYR[11]NT, induce reinstatement of cocaine seeking; (2) whether the effects of NT receptor activation on reinstatement can be modulated by D1/D5 or D2/D3 antagonists; (3) the specificity of the effects of NT receptor activation on the reinstatement of cocaine seeking. METHODS: In Experiment 1, rats were initially trained to self-administer cocaine. Following a subsequent period of extinction training, they were tested for the reinstatement of cocaine seeking by NT or D-TYR[11]NT (15, 30 microg i.c.v.). In Experiment 2, rats were pretreated with the D1/D5 antagonist, SCH 23390 (0.05, 0.10 mg/kg i.p.) or the D2/D3 antagonist, raclopride (0.25, 0.50 mg/kg i.p.), prior to testing for reinstatement by D-TYR[11]NT (15 microg i.c.v.). In Experiment 3, rats that had been trained to self-administer sucrose pellets were tested for the reinstatement of sucrose seeking by D-TYR[11]NT (15, 30 microg i.c.v.). RESULTS: (1) Both NT and D-TYR[11]NT produced robust reinstatement of cocaine seeking; (2) the effect of the analog was attenuated by pretreatment with the D1/D5, but not D2/D3, receptor antagonist; (3) the analog did not induce the reinstatement of sucrose seeking. CONCLUSIONS: The findings suggest that an interaction between NT and DA may contribute to the neurobiology of reinstatement in animals with a history of cocaine self-administration.
RATIONALE: Neurotensin (NT) has been implicated in some of the behavioral effects of psychostimulants. Thus, there is reason to think that NT may play a role in the reinstatement of cocaine seeking, and that it may do so via an interaction with dopamine (DA). OBJECTIVES: To assess (1) whether NT and an NT analog, D-TYR[11]NT, induce reinstatement of cocaine seeking; (2) whether the effects of NT receptor activation on reinstatement can be modulated by D1/D5 or D2/D3 antagonists; (3) the specificity of the effects of NT receptor activation on the reinstatement of cocaine seeking. METHODS: In Experiment 1, rats were initially trained to self-administer cocaine. Following a subsequent period of extinction training, they were tested for the reinstatement of cocaine seeking by NT or D-TYR[11]NT (15, 30 microg i.c.v.). In Experiment 2, rats were pretreated with the D1/D5 antagonist, SCH 23390 (0.05, 0.10 mg/kg i.p.) or the D2/D3 antagonist, raclopride (0.25, 0.50 mg/kg i.p.), prior to testing for reinstatement by D-TYR[11]NT (15 microg i.c.v.). In Experiment 3, rats that had been trained to self-administer sucrose pellets were tested for the reinstatement of sucrose seeking by D-TYR[11]NT (15, 30 microg i.c.v.). RESULTS: (1) Both NT and D-TYR[11]NT produced robust reinstatement of cocaine seeking; (2) the effect of the analog was attenuated by pretreatment with the D1/D5, but not D2/D3, receptor antagonist; (3) the analog did not induce the reinstatement of sucrose seeking. CONCLUSIONS: The findings suggest that an interaction between NT and DA may contribute to the neurobiology of reinstatement in animals with a history of cocaine self-administration.
Authors: Franca M Placenza; Paul J Fletcher; Susan Rotzinger; Franco J Vaccarino Journal: Psychopharmacology (Berl) Date: 2004-05-27 Impact factor: 4.530
Authors: Andrew T Gargiulo; Preeti S Badve; Genevieve R Curtis; Breanne E Prino; Jessica R Barson Journal: Psychopharmacology (Berl) Date: 2022-05-07 Impact factor: 4.415