Activation of central neurotensin receptors reinstates cocaine seeking in the rat: modulation by a D1/D5, but not D2/D3, receptor antagonist.
BACKGROUND
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).


OBJECTIVE
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.
Lopak
Vanessa
V
Centre for the Neurobiology of Stress, Departments of Life Science and Psychology, University of Toronto at Scarborough, Toronto, Ontario, M1A 1C4, Canada.
Erb
Suzanne
S
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D008297:Male; D009496:Neurotensin / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors*; D050641:Receptors, Dopamine D5 / Q000037:antagonists & inhibitors*; D018028:Receptors, Neurotensin / Q000187:drug effects* / Q000502:physiology; D013395:Sucrose / Q000008:administration & dosage
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D018028:Receptors, Neurotensin; D050641:Receptors, Dopamine D5; D009496:Neurotensin; D020891:Raclopride; D013395:Sucrose; D003042:Cocaine