Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats.
Level 5 - mechanism / opinion, no new human data
Preclinical animal research (intracranial self-stimulation in rats)
PubMed 30628811 · doi:10.1037/pha0000253
What was done
Male Sprague-Dawley rats were implanted with microelectrodes targeting the medial forebrain bundle and trained in a frequency-rate intracranial self-stimulation (ICSS) procedure. The authors evaluated the acute dose-effect and time-course effects of LSD, mescaline, and psilocybin on ICSS. They also tested whether repeated LSD administration altered its own ICSS effects, the abuse-related effects of methamphetamine, or the depressant effects of the kappa opioid receptor agonist U69,593.
What was found
The abstract reports no numerical values, effect sizes, or confidence intervals. It states that acute administration of LSD, mescaline, and psilocybin produced weak and inconsistent ICSS facilitation, with the predominant effect being dose- and time-dependent ICSS depression. Repeated LSD treatment did not alter its own ICSS depressant effects or methamphetamine-induced ICSS facilitation, but it attenuated U69,593-induced ICSS depression.
Why it matters
The findings provide preclinical evidence that classic 5-HT2A agonist hallucinogens show weak abuse-related facilitation in an established rodent model, while repeated LSD dosing may attenuate prodepressant kappa-opioid signaling.
Limits
This is an animal study in male rats, limiting direct translation to human clinical outcomes and female subjects. The abstract omits sample size, specific dosages, repeated-dosing schedules, and numerical statistics.
Cited by
- supports Mescaline, the active compound found in peyote, is a serotonin 5-HT2A receptor agonist.