Psychopharmacology
December 1, 2006
Kirsten Krebs-Thomson, Erbert M Ruiz, Virginia Masten et al.
96 citations
5-MeO-DMT, a hallucinogen similar to LSD, reduced movement, exploration, and startle responses in rats. These effects were blocked by a drug that targets serotonin 1A receptors but not by drugs that block serotonin 2A receptors, and only partially by a serotonin 2C blocker. This suggests that serotonin 1A receptors play a key role in the behavioral effects of 5-MeO-DMT, challenging the view that only serotonin 2 receptors are responsible for hallucinogenic effects.
Psychopharmacology
June 1, 2012
Adam L Halberstadt, David E Nichols, Mark A Geyer
55 citations
A combination of the hallucinogenic tryptamine 5-MeO-DMT and a monoamine oxidase inhibitor (MAOI) produces a biphasic effect on rat locomotor activity: an initial reduction followed by an increase. This study tested whether the delayed hyperactivity results from slowed metabolism of 5-MeO-DMT. A deuterated form of 5-MeO-DMT that resists MAO metabolism, when given alone at a higher dose (3.0 mg/kg), produced the same biphasic pattern as the 5-MeO-DMT/MAOI combination, while lower doses caused only hypoactivity. Receptor binding showed deuterium substitution did not alter 5-MeO-DMT's affinity for neurotransmitter sites. The findings indicate that MAO inhibition prolongs 5-MeO-DMT's occupation of central serotonin receptors, causing hyperactivity.
Psychopharmacology
November 1, 2008
Adam L Halberstadt, Mahalah R Buell, Virginia L Masten et al.
46 citations
The psychoactive tea ayahuasca contains DMT, 5-MeO-DMT, and MAO inhibitors harmine and harmaline. In rats, 5-MeO-DMT alone decreased movement and exploration. When combined with a low dose of harmaline, 5-MeO-DMT produced an initial decrease in locomotion followed by a later increase. This shift depended on inhibition of MAO-A, not MAO-B. The late hyperactivity was blocked by a 5-HT2A receptor antagonist, indicating that 5-HT2A receptors mediate this effect, while a 5-HT1A antagonist had no effect. Thus, harmaline alters 5-MeO-DMT's behavioral effects through MAO-A inhibition, and 5-HT2A receptors drive the delayed hyperactivity.
Pharmacology, biochemistry, and behavior
September 1, 2009
Vikas Duvvuri, Victoria B Risbrough, Walter H Kaye et al.
7 citations
A translational model of anorexia nervosa (AN) was tested using a hyponeophagia assay in mice, where food-deprived animals showed increased latency to begin feeding in a novel, anxiety-provoking environment. The non-selective serotonin agonist 5-MeODMT potentiated feeding inhibition beyond that caused by the environment alone, indicating a drug-by-environment interaction. Blocking the 5-HT(1A) receptor with WAY100635 reversed this effect, supporting a necessary role for 5-HT(1A) receptor activation in feeding inhibition. The findings suggest a mechanistic link between elevated 5-HT(1A) receptor activity and restricting-type AN, with implications for the interplay between anxiety and appetite suppression.
The international journal of neuropsychopharmacology
November 12, 2021
Benjamin Z Roberts, Arpi Minassian, Adam L Halberstadt et al.
People with HIV often develop cognitive problems linked to disrupted fronto-striatal brain circuits, which are also affected by cannabis. HIV transgenic rats, which model HIV-associated neurocognitive disorder, showed a significant prepulse inhibition deficit compared to healthy controls, mirroring the sensorimotor gating impairment seen in people with HIV. Acute treatment with THC (1 and 3 mg/kg) reduced prepulse inhibition in control rats but not in HIV transgenic rats, indicating a relative insensitivity to THC's disruptive effects on fronto-striatal function. Cannabidiol (1, 10, and 30 mg/kg) had only minor, genotype-independent effects on prepulse inhibition. This reduced sensitivity may help explain higher cannabis use rates among people with HIV.