Drug evaluations using neuronal networks cultured on microelectrode arrays

We used spontaneously active neuronal networks derived from dissociated emb ryonic murine spinal cord and auditory cortex and grown on substrate-integr ated thin-film microelectrodes to determine characteristic responses to the cannabinoid agonists anandamide (AN) and methanandamide (MA). AN and MA re versibly inhibited spike and burst production in both tissue types. Respons es of 21 cultures ranging in age from 23 to 111 days in vitro (d.i.v) showe d high intra- and inter-culture reproducibility at all ages. However, respo nses were tissue and substance-dependent. AN and MA were equipotent in cort ical cultures and terminated bursting and spiking at 2.5 +/- 0.9 muM (n = 1 0). Spinal cultures were shut-off by 1.3 +/- 0.7 muM (n = 15) AN, but requi red 5.8 +/- 1.2 muM MA for activity cessation. MA, but not AN, demonstrated a biphasic influence: excitation at 0.25-3.5 muM and suppression at 4-7.1 muM. Palmitoylethanolamide, a related lipophilic molecule with no reported binding to the CB1 receptor (to which AN and MA bind in the central nervous system), did not affect network activity at concentrations up to 6.5 muM. Irreversible cessation of activity was observed after 30 min applications o f AN or MA at > 7 muM. (C) 2000 Elsevier Science S.A. All rights reserved.