Interaction of LSD and other hallucinogens with dopamine-sensitive adenylate cyclase in primate brain: regional differences.
H S Ahn, M H Makman
Brain Research February 1, 1979 DOI: 10.1016/0006-8993(79)90757-1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro biochemical study Peer reviewed |
|---|---|
| Population | Cebus and rhesus monkey brain tissue homogenates (anterior limbic cortex, frontal cortex, caudate nucleus, auditory cortex) and retina |
| Interventions | D-lysergic acid diethylamide (LSD) mescaline methamphetamine dopamine haloperidol fluphenazine phentolamine |
| Topics | LSD Mescaline |
| Keywords | Brain Limbic system Caudate nucleus Frontal lobe Auditory cortex Retina Animals Haplorhini Macaca mulatta Methamphetamine Haloperidol Phentolamine Fluphenazine Receptors, dopamine Drug interactions Adenylyl cyclases |
| Key points | LSD and mescaline stimulated dopamine-sensitive adenylate cyclase in anterior limbic cortex and auditory cortex but not in frontal cortex, caudate nucleus, or retina, with LSD about ten times more potent than mescaline (EC50 0.43 vs 4.5 micromolar) and both producing about 70% maximal stimulation. LSD competitively antagonized dopamine-stimulated activity in all brain regions examined. The authors propose that this region-specific dopamine agonist action may contribute to the behavioral effects of LSD, mescaline, and methamphetamine in primates. |
Abstract
The influence of D-lysergic acid diethylamide (LSD) and mescaline on adenylate cyclase activity was studied in homogenates of Cebus and rhesus monkey anterior limbic cortex (ALC), frontal cortex (FC), caudate nucleus and retina. Previous studies have shown these tissues to contain dopamine-stimulated adenylate cyclase (AC). In addition, we are now reporting the presence of a dopamine-sensitive adenylate cyclase in the auditory cortex. AC of ALC and auditory cortex was stimulated by LSD and mescaline, whereas activity of FC, caudate nucleus and retina was not stimulated by the same agents. In contrast to regional specificity for stimulation, LSD was capable of antagonizing dopamine-stimulated activity in all brain regions examined. LSD and mescaline produced similar maximal stimulation (about 70%) of AC of ALC homogenates, but the EC50 for LSD (0.43 micrometer) was about one-tenth that for mescaline (4.5 micrometer). Similar relative potencies were also observed for the auditory cortex enzyme. Although much weaker than LSD, methamphetamine also produced a dose-dependent stimulation of ALC AC. Both agonist and antagonist effects of the hallucinogens appear to involve interaction with dopamine receptors; LSD- or methamphetamine-stimulated activity in ALC was blocked by haloperidol and fluphenazine, which are dopamine antagonists, but not by phentolamine, an alpha-receptor blocker. Antagonism of dopamine by LSD in both ALC and FC was found to be competitive and mescaline was an effective but weaker antagonist than was LSD. In addition, neither histamine--nor Gpp(NH)p--stimulated activity of FC was inhibited by LSD. It is proposed that the occurrence of dopamine agonistic action of hallucinogens in only certain regions of primate brain may provide a basis for at least some of the behavioral effects of LSD, mescaline and methamphetamine in primates.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 10
- Dose-Response Study of N,N-Dimethyltryptamine in Humans Archives of General Psychiatry February 1, 1994
- Hallucinogenic Drugs in Psychiatric Research and Treatment Perspectives and Prospects The Journal of Nervous and Mental Disease March 1, 1995
- Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose Psychopharmacology October 6, 2007
- Lysergic acid diethylamide (LSD) is a partial agonist of D2 dopaminergic receptors and it potentiates dopamine-mediated prolactin secretion in lactotrophs in vitro Life Sciences June 1, 1998
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
and 5 more in the library
Cites 3
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- Lysergic acid diethylamide: evidence for stimulation of cerebral dopamine receptors Brain Research August 1, 1975
- Interactions between lysergic acid diethylamide and dopamine-sensitive adenylate cyclase systems in rat brain Brain Research August 1, 1975