Involvement of adenosine in the effect of antidepressants on glutamate and aspartate release in the rat prefrontal cortex

Abstract.

The effect of local administration of amitriptyline (AMI), desipramine (DMI) and citalopram (CIT) on veratridine-evoked glutamate (Glu) and aspartate (Asp) release in the prefrontal cortex of the conscious rat was examined using in vivo reverse microdialysis. The antidepressants (each at 100 µM) significantly reduced Glu and Asp release. The effect of AMI and CIT was attenuated by i.p. administration of the adenosine A₁/A_2A receptor antagonist caffeine (10 mg/kg), or by local infusion of the adenosine A₁ receptor antagonist 8-cyclopentyltheophylline (CPT, 75 µM). Neither caffeine nor CPT influenced the effect of DMI (100 µM). The inhibitory action of DMI at a lower concentration (50 µM) was diminished significantly by CPT, but not caffeine. Perfusion of 5-hydroxytryptamine (5-HT; 100 µM) and the selective agonist of adenosine A₁ receptors N ⁶-cyclopentyladenosine (CPA; 50 and 100 µM) also suppressed Glu and Asp release. It is suggested that the blockade of the cellular uptake of adenosine, or indirect enhancement of its release, and subsequent activation of adenosine A₁ receptors may be responsible for the inhibitory effect of antidepressants on Glu and Asp release.