Modulation of electrically evoked acetylcholine release through cannabinoid cb1 receptors: evidence for an endocannabinoid tone in the human neocortex
Section snippets
Experimental procedures
Fresh human neocortical tissue, to be removed in order to gain access to the pathological areas (subcortical brain tumors or epilepsy regions), was obtained from 47 patients (age 6–76 years) during gentle, atraumatic surgical treatment to ensure tissue viability. Before the operation every patient was informed and signed a declaration of consent, as requested by the local ethics committee of the University Hospital of Freiburg. Tissue macroscopically infiltrated with tumor was excluded, i.e.
Mouse neocortex
ACh release was evoked with a stimulation frequency of 0.1 Hz to preclude any autoinhibition feedback of the released transmitter (Albrecht et al., 1999). In the presence of hemicholinium (10 μM) throughout superfusion the electrically evoked [3H]-ACh release from mouse neocortical slices resulted in a mean S1 value of 1.44% of tissue tritium ([1.36%, 1.52%], n=193). None of the drugs used had an effect on basal [3H]-outflow since the b2/b1 and b3/b1 ratios did not differ from controls (data
Discussion
The present study examined the effects of synthetic cannabinoids on electrically evoked ACh release and their interactions with endogenous ligands. Evoked tritium overflow from mice (Jehle et al., 2000) and human (Feuerstein et al., 1990) neocortical slices has been shown earlier to be tetrodotoxin-sensitive and calcium-dependent and to represent the release of endogenous ACh (Feuerstein et al., 1998). Thus, quasi-physiological transmitter release can be assumed. Hemicholinium was routinely
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft (SFB 505, TP C8).
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