Infusion of the substance P analogue, DiMe-C7, into the ventral tegmental area induces reinstatement of cocaine-seeking behaviour in rats.
BACKGROUND
The mesocorticolimbic dopamine (DA) system is critically involved in mediating reinstatement of drug-seeking behaviour. Substance P (SP) is a neuropeptide that significantly interacts with the mesocorticolimbic system, therefore suggesting a possible role for the SP system in the mediation of relapse.


OBJECTIVE
This study examined the effects of injections of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) on reinstatement of cocaine-seeking behaviour, as well as on locomotor activity in rats. Additionally, this study examined whether these effects are DA-dependent.


METHODS
Rats were trained to self-administer cocaine for 15 days followed by 15 days of extinction. Reinstatement of cocaine-seeking behaviour was then measured in response to bilateral intra-VTA microinjections of DiMe-C7 (0, 0.1, 0.5 and 2.5 microg). In a separate group of rats, locomotor activity was measured in response to intra-VTA injections of DiMe-C7 (0, 0.5, 1.5 and 3 microg). The effects of pre-treatment with DA receptor antagonists on DiMe-C7-induced reinstatement and locomotor activity were also examined. Animals were pre-treated with the D(1) and D(2) receptor antagonists, SCH23390 and haloperidol (0, 0.01 and 0.03 mg/kg, IP), respectively, prior to receiving intra-VTA injections of DiMe-C7 (0 and 2.5 microg).


RESULTS
Infusion of DiMe-C7 into the VTA increased locomotor activity and induced reinstatement of cocaine-seeking behaviour. Both SCH23390 and haloperidol blocked intra-VTA DiMe-C7-induced locomotor activation. In addition, SCH23390 attenuated DiMe-C7-induced reinstatement of cocaine-seeking behaviour, while haloperidol had no effect.


CONCLUSIONS
These results suggest that interactions between SP and the mesocorticolimbic DA system may play a role in mediating reinstatement of cocaine-seeking behaviour and that the involvement of these interactions in reinstatement are dependent upon D(1) receptor mechanisms.
Placenza
Franca M
FM
Department of Psychology, University of Toronto, Toronto, ON, Canada, M5S 3G3.
Fletcher
Paul J
PJ
Rotzinger
Susan
S
Vaccarino
Franco J
FJ
D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced*; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage*; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D013373:Substance P / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D010446:Peptide Fragments; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D003042:Cocaine; D011761:Pyrrolidonecarboxylic Acid