Rewarding effects elicited by cocaine microinjections into the ventral tegmental area of C57BL/6 mice: involvement of dopamine D1 and serotonin1B receptors.
BACKGROUND
The role of ventral tegmental area (VTA) in mediating the rewarding effects of cocaine has not been extensively studied.


OBJECTIVE
We used the intracranial self-administration (ICSA) procedure to assess the involvement of the VTA in the rewarding effects of cocaine, and the effect of dopamine (DA) D(1)- and serotonin (5-HT)(1B)-receptor antagonists on ICSA of cocaine.


METHODS
Adult male C57BL/6 mice were stereotaxically implanted, unilaterally, with a guide cannula either 1.5 or 2.3 mm above the VTA. After 1 week, mice were trained to discriminate between the two arms of a Y-maze over seven daily sessions, one arm being reinforced by intracranial cocaine microinjections. Starting from session 8, the D(1) and 5-HT(1B)-receptor antagonists were injected IP pre-test each day over five consecutive sessions.


RESULTS
Mice injected into the VTA rapidly exhibited a preference for the cocaine-reinforced arm, whatever the dose of cocaine available (30 pmol or 150 pmol per injection), reaching optimum ICSA performance within 5 days. In contrast, mice injected 0.8 mm above the VTA did not discriminate between the arms of the maze and performed at random, except for one subject. Once the ICSA response was acquired, systemic pre-injections of either the D(1) (SCH23390; 25 microg/kg IP) or 5-HT(1B) (GR127935; 0.5 mg/kg IP) antagonist disrupted this behavior. Replacement of each antagonist by vehicle led to the reinstatement of intra-VTA cocaine self-administration.


CONCLUSIONS
The results of the present study suggest that VTA neurons play a critical role in mediating the rewarding effects of acute cocaine and that both D(1) and 5-HT(1B) receptors modulate these effects.
David
Vincent
V
Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Université de Bordeaux I, Avenue des Facultés, 33405 Talence Cedex, France. v.david@lnc.u-bordeaux1.fr
Segu
Louis
L
Buhot
Marie-Christine
MC
Ichaye
Marina
M
Cazala
Pierre
P
D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections / Q000379:methods; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D012201:Reward; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology; D013037:Spatial Behavior / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D000779:Anesthetics, Local; D001552:Benzazepines; D018492:Dopamine Antagonists; D010069:Oxadiazoles; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D017447:Receptors, Dopamine D1; D012702:Serotonin Antagonists; C090701:GR 127935; D003042:Cocaine