Injections of the psychedelic drug lysergic acid diethylamide, commonly known as LSD or acid, accelerates Pavlovian learning in rabbits by desensitizing certain neurotransmitter receptors, according to a published report.
The study, which was lead by Anthony G. Romano of the Drexel University College of Medicine, demonstrated that LSD can enhance the acquisition of eyeblink conditioning by desensitizing specific serotonin receptors located in the dorsal hippocampus, a region of the brain associated with learning and memory.
“The serotonin 2A receptor (5-HT2A) has been implicated in the production of hallucinations in humans and cognitive effects such as enhanced acquisition during autoshaping in rodents, enhanced acquisition of trace eyeblink conditioning in the rabbit, and enhanced working memory in the non-human primate,” the authors of the study write.
Eyeblink conditioning is a type of Pavlovian conditioning that involves pairing an auditory or visual stimulus with an eyeblink-eliciting stimulus, such as a small puff of air to the eye. After repeatedly pairing an auditory or visual stimulus with an eyeblink-eliciting stimulus, the animal eventually learns associate the two stimuli and will blink after being presented with only the auditory or visual stimulus.
This type of conditioning is used by researchers to investigate the neural mechanisms that underlie learning and memory.
In their study, Romano and his colleagues injected either LSD or artificial cerebrospinal fluid into the dorsal hippocampus of rabbits twenty minutes before eight daily conditioning sessions. The sessions each consisted of 60 pairings of a tone with a puff of air to the rabbit’s eye.
Rabbits injected with LSD showed a small but statistically significant acceleration of learning as compared to rabbits that were injected with artificial cerebrospinal fluid. In addition, rabbits injected with higher doses of LSD showed a greater acceleration of learning compared to those injected with lower doses.
Romano and his colleagues determined that LSD produced a selective desensitization of the 5-HT2A receptor by injecting another psychedelic drug, dimethoxy-iodophenyl-aminopropane hydrocloride (DOI), into the hippocampus of the rabbits after the eight conditioning sessions were over.
DOI, like LSD, binds to the 5-HT2A receptor and produces a head bobbing motion in rabbits. The rabbits that had been injected with LSD during the conditioning sessions showed lower levels of head bobbing motion than those that had not been injected with LSD, suggesting that the chronic injection of LSD desensitized the 5-HT2A receptor.
Rabbits provide an excellent animal model for predicting the effects of drugs that act on 5-HT2A receptors in humans, according to the authors of the study, suggesting LSD may have a similar effect in humans.
“This study supports the current view that hallucinogens act at the 5-HT2A receptor and suggest an important role for 5-HT2A receptors located in the hippocampus in the regulation of cognitive and motoric behaviors,” the authors of the study concluded. “These results may provide additional clues for the role of these receptors in schizophrenia and in the actions of antipsychotic drugs.”
Romano and his colleagues’ study was published in volume 212 of Psychopharmacology in September of 2010 and received funding from the National Institute of Mental Health.