Prior Treatment (Priming) with Caffeine Sensitizes D2-Dopamine-Mediated Contralateral Rotational Behavior in 6-Hydroxydopamine-Lesioned Rats

Abstract

Background/Aims: In unilaterally dopamine-depleted rats, repeated treatment with dopamine agonists sensitizes contralateral rotational behavior. Since A2a adenosine receptors are co-localized with D2 dopamine receptors in the brain, it was hypothesized that repeated treatment with the adenosine antagonist caffeine could sensitize D2 dopamine-mediated rotational behavior. Methods: Rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA), and pretreated (primed) with 3 injections of caffeine or water. One week later, rats were challenged with the D2 agonist quinpirole (0.25 mg/kg). Results: 6-OHDA rats primed with caffeine (50 mg/kg) displayed contralateral rotational behavior following challenge with quinpirole – an effect not observed with caffeine (10 or 75 mg/kg) or water. Conclusions: These results suggest that prior administration of caffeine can sensitize D2 dopamine-mediated rotational behavior in dopamine-depleted rats.

Mechanisms of the psychostimulant effects of caffeine: implications for substance use disorders

“…Hence, unless previous sensitization of a direct dopamine receptor has been established, caffeine behaves as an indirect dopamine receptor agonist and tends to produce ipsilateral turning (Fenu and Morelli 1998; Cauli et al 2003). The other way around, repeated but intermittent (non-daily) systemic caffeine administration, a schedule that is not associated with tolerance to its psychostimulant effects, sensitizes the rat to the contralateral and ipsilateral turning induced by direct and indirect dopamine receptor agonists, respectively (Cauli et al 2003, 2005; Pollack et al 2010). …”

Caffeine Protects Dopaminergic Neurons From Dopamine-Induced Neurodegeneration via Synergistic Adenosine-Dopamine D2-Like Receptor Interactions in Transgenic Caenorhabditis elegans

“…In one study, it was shown that caffeine—by antagonizing A R s—sensitized dopamine D2 receptors normally co-localized with them in the rat brain, leading to contralateral rotational behavior after exposure to 6-hydroxydopamine (6-OHDA). In this way, they proposed that caffeine may in fact worsen dopamine-related neurotoxicity and motor dysfunction (Pollack et al, 2010 ). Further, the pathological rotational behavior in rats was also suggestive of possible depletion of brain dopamine, which parallels to neurodegeneration (Willis and Sandyk, 1993 ).…”