Drug evaluations using neuronal networks cultured on microelectrode arrays.
We used spontaneously active neuronal networks derived from dissociated embryonic murine spinal cord and auditory cortex and grown on substrate-integrated thin-film microelectrodes to determine characteristic responses to the cannabinoid agonists anandamide (AN) and methanandamide (MA). AN and MA reversibly inhibited spike and burst production in both tissue types. Responses of 21 cultures ranging in age from 23 to 111 days in vitro (d.i.v.) showed high intra- and inter-culture reproducibility at all ages. However, responses were tissue and substance-dependent. AN and MA were equipotent in cortical cultures and terminated bursting and spiking at 2.5 +/- 0.9 microM (n = 10). Spinal cultures were shut-off by 1.3 +/- 0.7 microM (n = 15) AN, but required 5.8 +/- 1.2 microM MA for activity cessation. MA, but not AN, demonstrated a biphasic influence: excitation at 0.25-3.5 microM and suppression at 4-7.1 microM. Palmitoylethanolamide, a related lipophilic molecule with no reported binding to the CBI receptor (to which AN and MA bind in the central nervous system), did not affect network activity at concentrations up to 6.5 microM. Irreversible cessation of activity was observed after 30 min applications of AN or MA at > 7 microM.
Morefield
S I
SI
Department of Biological Sciences and Center for Network Neuroscience, University of North Texas, Denton 76203, USA.
Keefer
E W
EW
Chapman
K D
KD
Gross
G W
GW
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001303:Auditory Cortex / Q000187:drug effects* / Q000502:physiology; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D063388:Endocannabinoids; D051379:Mice; D008813:Mice, Inbred ICR; D008839:Microelectrodes; D009415:Nerve Net / Q000187:drug effects* / Q000502:physiology; D009928:Organ Specificity; D053284:Polyunsaturated Alkamides; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C088155:methanandamide; C078814:anandamide; D001640:Bicuculline