Related Experiment Video
Updated: Jun 26, 2026

Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats
Published on: August 24, 2016
Caffeine and a selective adenosine A2A receptor antagonist induce reward and sensitization behavior associated with
Chih W Hsu1, C Y Chen, Chin-Shine Wang
1Department of Emergency Medicine, Tzu Chi General Hospital, Hualien 970, Taiwan. saab30002000@yahoo.com.tw
Rationale:
Caffeine, an antagonist of adenosine A(1) and A(2A) receptor, is the most widely used psychoactive substance in the world. Evidence indicates that caffeine interacts with the neuronal systems involved in drug reinforcing. Although adenosine A(1) and/or A(2A) receptor have been found to play important roles in the locomotor stimulation and probably reinforcing effect of caffeine, the relative contribution of the A(1) and/or A(2A) receptors to the acute and chronic motor activation and reinforcing effects of caffeine has not been completely investigated.
Objective:
The roles of adenosine A(1) and/or A(2A) receptor and the association of phospho-Thr75-dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) in the motor activation and reinforcing effects of caffeine, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A(1) antagonist, and 5-amino-7-(beta-phenylethyl)-2-(8-furyl) pyrazolol [4,3-e]-1,2,4-triazolol [1,5-c] pyrimidine (SCH58261), a selective A(2A) receptor antagonist were examined.
Methods:
Locomotor stimulation and behavioral sensitization of caffeine, DPCPX, and SCH58261 were studied in C57BL/6 male mice following acute and chronic administration. Conditioned place preference (CPP) paradigm was used to evaluate the drug-seeking potential of these compounds. Furthermore, the expression of phospho-Thr75-DARPP-32 in striatal membrane from behaviorally sensitized mice was analyzed by Western blot.
Results:
Caffeine and SCH58261 but not DPCPX induced CPP and locomotor sensitization in C57BL/6 mice. The locomotor sensitization after chronic treatment was associated with increased DARPP-32 phosphorylation at Thr75 in the striatum.
Conclusion:
Caffeine-induced reinforcing effect and behavioral sensitization are mediated by antagonism at adenosine A(2A) receptor. These effects are associated with phosphorylation of DARPP-32 at Thr75 in the striatum.
Related Concept Videos
Adrenergic Agonists: Indirect-Acting Agents
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
Stimulants
Cocaine can be administered via snorting, injection, or smoking. It primarily functions by blocking the reuptake of dopamine, resulting in a euphoric high characterized by an intense sensation of happiness and...
Drugs Affecting Neurotransmitter Release or Uptake
Adrenergic Agonists: Chemistry and Structure-Activity Relationship
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
GPCRs Regulate Adenylyl Cylase Activity
Two...
Adrenergic Agonists: Direct-Acting Agents
These agents can be classified...

