TY - JOUR
T1 - Some behavioral effects of hallucinogens are mediated by a postsynaptic serotonergic action
T2 - Evidence from single unit studies in freely moving cats
AU - Heym, James
AU - Rasmussen, Kurt
AU - Jacobs, Barry L.
N1 - Funding Information:
This research was supported by National Institute of Mental Health grant MH 23433 (B.L.J.) and National Research Service Award NS 06269 (J.H.). The authors wish to thank Organon, Inc. (mianserin), Schering AG (lisuride), Farmitalia (metergoline), and Janssen Pharmaceuticals (ketanserin) for their generous gift of drugs. The authors also extend their gratitude to Ms. Dorothy Millen for her excellent technical assistance and to Ms. Arlene Kronewitter for preparation of this manuscript.
PY - 1984/5/18
Y1 - 1984/5/18
N2 - Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 μg/kg) or DOM (250 μg/kg) but not that resulting either from lisuride (50 μg/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic synaptic effect unaffected. Thus, the behavioral and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.
AB - Although central serotonergic systems appear to be linked importantly to the mechanism of action of a variety of hallucinogenic drugs, the nature of this interaction has remained unclear. In the present study, the question of whether the critical link is presynaptic or postsynaptic was examined in cats. Behaviorally inactive doses (1.0 mg/kg) of the serotonin receptor antagonists mianserin, ketanserin or metergoline effectively blocked behavior, as measured by the cat limb flick response, elicited by either LSD (50 μg/kg) or DOM (250 μg/kg) but not that resulting either from lisuride (50 μg/kg) or a high dose of apomorphine (4 mg/kg). Pretreatment with 1.0 mg/kg of mianserin, which completely attenuated LSD's behavioral effect, failed to alter LSD-induced depression of mesencephalic serotonergic neuron discharge. These results demonstrate that at least some of the behavioral effects of LSD can be blocked by pharmacological antagonism of postsynaptic serotonin receptors which leaves LSD's presynaptic synaptic effect unaffected. Thus, the behavioral and possibly psychoactive, effects of hallucinogens appear to be attributable to an action at 5HT2 receptors, presumably located postsynaptically.
KW - Cat behavior
KW - Hallucinogens
KW - Raphe unit activity
KW - Serotonergic neurons
KW - Serotonin antagonists
KW - Serotonin receptors
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U2 - 10.1016/0014-2999(84)90030-X
DO - 10.1016/0014-2999(84)90030-X
M3 - Article
C2 - 6745319
AN - SCOPUS:0021215170
SN - 0014-2999
VL - 101
SP - 57
EP - 68
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-2
ER -