The Lack of A(2A) Adenosine Receptors
Diminishes the Reinforcing Efficacy of Cocaine
by
Soria G, Castane A, Ledent C, Parmentier M, Maldonado R, Valverde O.
1Laboratori de Neurofarmacologia,
Departament de Ciencies Experimentals i de la Salut,
Universitat Pompeu Fabra, Barcelona, Spain.
Neuropsychopharmacology. 2005 Aug 17
ABSTRACTAdenosine is an endogenous purine nucleoside, which acts as a neuromodulator in the central nervous system. A(2A) adenosine and D(2) dopamine receptors are colocalized in the same neurons in discrete brain areas, and the dopaminergic transmission plays a crucial role in the addictive properties of drugs of abuse, such as cocaine. In the present study, we have investigated the specific role of A(2A) adenosine receptors in cocaine-induced behavioral responses related to its addictive properties. For this purpose, we have evaluated the acute locomotor effects produced by cocaine and the development of locomotor sensitization by repeated cocaine administration. In addition, we have also examined cocaine acute rewarding properties using the conditioned place preference. Finally, we used the intravenous drug self-administration paradigm to investigate the acquisition of an operant response maintained by cocaine self-administration and the reinforcing efficacy of the drug in these knockout animals. Acute cocaine induced a similar increase of locomotor activity in mice lacking A(2A) adenosine receptors and wild-type littermates. Cocaine-induced locomotor sensitization and conditioned place preference were also maintained in A(2A) knockout mice. Nevertheless, these knockout mice showed a lower rate of cocaine self-administration than wild-type mice in both fixed ratio 1 and 3 schedules of reinforcement. Moreover, a reduction in the maximal effort to obtain a cocaine infusion was found in A(2A) knockout mice under a progressive ratio schedule. In addition, a vertical shift of the cocaine dose-response curve was observed in mice lacking A(2A) adenosine receptors in comparison with wild-type littermates. Our study demonstrates that A(2A) adenosine receptors play an important role in cocaine addictive properties, and these receptors seem to be required to develop the addictive effects of this drugCART
Cocaine
Dopamine
Norcocaine
Metabolism
Cocaine hotspots
Cocaine withdrawal
The coke-craving brain
The neural basis of addiction
Freebasing flies go hyperkinetic
Cocaine, alcohol and cocaethylene
Cocaethylene and cocaine dependence
01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24
Refs
HOME
HedWeb
Future Opioids
BLTC Research
Utopian Surgery?
The Hedonistic Imperative
MDMA: Utopian Pharmacology
When Is It Best To Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family
