Sensitization to cocaine is inhibited after intra-accumbal GR103691 or rimonabant, but it is enhanced after co-infusion indicating functional interaction between accumbens D(3) and CB1 receptors.
BACKGROUND
Dopamine D(3) receptors and cannabinoid CB(1) receptors are both expressed in the nucleus accumbens, and they have been involved in motor sensitization to cocaine. The objectives were: (1) to study the effects of blockade of these receptors on sensitization to repeated cocaine, by using GR103691, D(3) receptor blocker, and rimonabant, CB(1) receptor ligand, and (2) to discern if both receptors interact by co-infusing them.


METHODS
Cocaine (10 mg/kg) was injected daily for 3 days (induction phase) and later on day 8 (expression phase), and locomotor activity was measured during 2 h after cocaine. GR103691 and rimonabant were bilaterally injected (0.5 μl volume of each infusion) in the nucleus accumbens through cannulae (GR103691, 0, 4.85, and 9.7 μg/μl; rimonabant, 0, 0.5, and 1.5 μg/μl), before cocaine, during either induction or expression phases of sensitization.


RESULTS
The findings indicated that sensitizing effects of cocaine were abolished after D(3) receptor blocking during both induction and expression phases, as well as rimonabant infusion during the expression (not induction) phase. A functional interaction between both receptors was also observed, because if GR103691 was injected during induction and rimonabant during expression, sensitizing effects of cocaine were observed to be normal or further enhanced.


CONCLUSIONS
Dopamine D(3) receptors within the nucleus accumbens are critical for the development and consolidation of sensitization, and cannabinoid CB(1) receptors are critical for the expression of sensitization. Co-blockade of D(3) and CB(1) receptors exert opposite effects to blockade of these receptors separately, revealing the existence of a functional interaction between them.
Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, Av. Sanchez Pizjuan 4, 41009, Sevilla, Spain.
Susana
S
Ramiro-Fuentes
Emilio
E
Fernandez-Espejo
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D054314:Drug Inverse Agonism; D004357:Drug Synergism; D057967:Infusions, Intraventricular; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D000077285:Rimonabant
D001713:Biphenyl Compounds; D010879:Piperazines; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050637:Receptors, Dopamine D3; C105771:GR 103691; D003042:Cocaine; D000077285:Rimonabant