Purinergic regulation of brain catecholamine neurotransmission: In vivo electrophysiology and microdialysis study in rats

Abstract

Abstract. It was previously reported that adenosine-2A (A 2A ) receptors interact with dopamine-2 (D 2 ) receptors on a molecular level. The aim of the current study was to investigate the functional output of this interaction. In vivo microdialysis was used to assess the effects of an antagonist of A 2A receptors, ZM 241385, and an antagonist of D 2 receptors haloperidol, either alone or in combination, on brain catecholamine levels. It was found that ZM 241385 did not alter catecholamine levels by its own, but potentiated haloperidol-induced dopamine and norepinephrine release in the nucleus accumbens and prefrontal cortex, respectively. In vivo electrophysiology was used to assess the effect of an agonist (CGS 216820) and an antagonist (ZM 241385) of A 2A receptors on the excitability of dopamine and norepinephrine neurons. It was found that CGS 216820 dose-dependently inhibited dopamine and norepinephrine neurons and ZM 241385 reversed this inhibition. In conclusion, those A 2A receptors modulate brain catecholamine transmission, and this modulation is mediated, at least in part, via the regulation of excitability of norepinephrine and dopamine neurons. The ability of antagonists of A 2A receptors to potentiate the effect of haloperidol on brain norepinephrine and dopamine levels may enhance its clinical efficacy as an antipsychotic drug.

Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors

“…Norepinephrine neurons were recorded from the locus coeruleus (LC), 8.0–8.3 mm posterior to bregma, 1.2–1.4 mm lateral to the midline, and 5.5–7.5 mm ventral to the brain surface [26]. Norepinephrine neurons were recognized by regular firing rate of 0.5–5.0 Hz, positive action potential of long duration of 0.8–1.2 msec and a characteristic burst discharge in response to nociceptive pinch of the contralateral hind paw, as described in our previous studies [32,46,47,48]. After a norepinephrine neuron was identified and its basal firing activity was recorded for 2 min, SMe1EC2M3 was administered intravenously (i.v.)…”

Adenosine A2A receptors modulate the dopamine D2 receptor‐mediated inhibition of synaptic transmission in the mouse prefrontal cortex

“…In fact, we observed that the selective A 2A R antagonist SCH58261 attenuated the D 2 R‐mediated inhibition of glutamatergic transmission in the PFC. Likewise, this inhibitory effect of dopamine was also reduced upon genetic deletion of A 2A R. This electrophysiological evidence is in notable agreement with a previous microdialysis study reporting an ability of A 2A R antagonists to attenuate D 2 R‐mediated effects in the PFC (Dremencov et al ., ). Our combined neurochemical evidence, identifying the co‐localization of A 2A R and D 2 R in glutamatergic nerve terminals (Fig.…”

“…Additionally, A 2A R can synergize with D 1 R in the hippocampus to control memory performance (Tyebji et al ., ). However, despite their parallel ability to control PFC‐dependent behavioural responses, the potential interplay between A 2A R and dopamine receptors has been seldom explored in the PFC (Pardo et al ., ; Dremencov et al ., ). Thus, we now tested whether the pharmacological or genetic manipulation of A 2A R affects the ability of dopamine to control glutamatergic synaptic transmission in the PFC.…”

Maternal Deprivation Induces Memory Deficits That Are Reduced by One Aerobic Exercise Shot Performed after the Learning Session

“…Although the HPLC technique used in our study had been previously used [33, 43], it is important to consider that the degradation of DA and NE can occur from 200 to 2000 milliseconds [52], which made their measurement difficult. So, measurements by in vivo microanalysis may provide more reliable results [60].…”