The effects of caffeine on adenosine and dopamine receptor density in rat striatum

Brian Nolan, Kathy O'Boyle. UCD School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin, Ireland.

Caffeine is an adenosine receptor antagonist with marked psychomotor stimulant effects. Substantial evidence suggests that the motor stimulant effects of caffeine are mediated, at least in part, by antagonistic interactions between specific adenosine and dopamine receptor subtypes located in the basal ganglia (Ferre et al, 1997). Studies have shown that treatment of pregnant rats with caffeine caused a 30-50 % down-regulation in the expression of the A 1 receptor in mothers and full-term foetuses, ( Leonet al, 2002). This study examines the effect of caffeine on the density of A 1 A 2A, D 1 and D 2 receptors.

Male wistar rats (150-250 g) were injected i.p. with 100 mg/kg caffeine on four consecutive days. The control group received saline. All animals were killed 14 days post treatment and the striata were dissected out. Saturation binding experiments were used to determine the densities of A 1, A 2A, D 1 and D 2 receptors in both groups. [ 3H] DPCPX (0.07-2.54 nM) was used to label A 1 receptors and 1 µM CPA was to determine non-specific binding. For the A 2A, D 1 and D 2 receptors [ 3H] ZM 241385 (0.13-5.6 nM) and SCH 58261 (1 µM), [ 3H] SCH 23390 (0.06-2 nM) and flupentixol (1 µM), and [ 3H] spiperone (0.06-2 nM) and domperidone (1 µM) were used to determine receptor density and non-specific binding, respectively .

All radioligands bound to a single, saturable population of sites. Receptor density (B MAX) and apparent dissociation constant (K D) values were obtained for all four receptors in both groups (Table 1). Control values correlated with those found previously. No significant differences between control and caffeine treated groups were found for any receptor examined (p > 0.05; t test).

Table 1. Effect of caffeine on receptor density and affinity in rat striatum

m ± SEM, n= 4 for all conditions. B MAX in fmol/mg tissue; K D in nM

These results indicate that under the conditions employed in this study, caffeine administration to rats did not alter the density of A1 A2A, D1 or D2 receptors in striatal tissue.

Ferre S et al, (1997) Trends Neurosci 20: 482-487
Leon D et al, (2002) J Neurochem 82: 625-34

This work was supported by Enterprise Ireland and University College Dublin.