The discriminative stimulus properties of LSD: Mechanisms of action☆
1978; Elsevier BV; Volume: 17; Issue: 4-5 Linguagem: Inglês
10.1016/0028-3908(78)90109-0
ISSN1873-7064
AutoresDeborah J. Kuhn, Frances V. White, Jens Appel,
Tópico(s)Neuroendocrine regulation and behavior
ResumoThe CNS correlates of d-lysergic acid diethylamide (LSD) actions were investigated by means of a sensitive and specific behavioural assay procedure. Rats were trained to discriminate D-LSD from saline in two lever operant chambers. After intraperitoneal injections of 0.08 mg/kg of LSD, reinforcement could be obtained only by responding on one particular lever (left or right); responding on the opposite lever was reinforced only after saline injections. Once the LSD and saline exerted reliable stimulus control over lever choice (85% correct), rats were tested with various agents which alter the functional activity of the transmitter-containing neuronal systems. l-Tryptophan, chlorimipramine and fluoxetine, all of which increase the synaptic availability of serotonin, neither blocked nor, by themselves, mimicked (transferred to) LSD. However, quipazine, a putative serotonin agonist, produced an almost complete (78%) transfer to LSD. The presumed serotonin antagonists: methiothepin, 2-bromo-D-lysergic acid diethylamide, methysergide, cyproheptadine and cinanserin, blocked the LSD cue in a dose-related manner. The potent dopamine antagonists: haloperidol, fluphenazine, trifluoperazine, α-flupenthixol, and (+)-butaclamol, were without effect on the discriminability of LSD as were α- and β-adrenergic, cholinergic and histaminergic antagonists. Apomorphine, a dopamine agonist, produced a partial transfer to LSD. These data indicate that the discriminative stimulus properties of LSD may be mediated by post-synaptic serotonin or LSD receptors. Dopamine receptors did not seem to be involved in the LSD stimulus cue.
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