Comparative acute effects of LSD and psilocybin were assessed in rats. Both drugs were administered at t = 0 h. Data are expressed as mean + SEM for 28 subjects. Maximal effects are presented in Supplementary Table S5.
Dopamine D4 receptor involvement in discriminative stimulus effects in rats of LSD
Dopamine D4 receptor involvement in the discriminative stimulus effects of psilocybin vs LSD has been studied by Van Tol and colleagues. The researchers used HEK cell lines stably expressing the human D4.4 dopamine receptor to investigate the effects of LSD and Psilocibin on the brain. Interestingly, these compounds both inhibit forskolin-stimulated cAMP production by inhibiting the D4 receptor.
The researchers employed a behavioral paradigm known as drug discrimination in rats. In this paradigm, rats learn to discriminate between drug and non-drug solutions by pressing a lever. This correct response produces a reinforcement.
The D4 receptor mediates changes in neuronal excitability and synaptic plasticity and has been implicated in integrative brain functions. Its expression is high in the anterior cingulate gyrus and throughout the frontal cortex.
These results support the findings of Freedman (1984), who reported that serotonergic hallucinogens have time-dependent phases. This means that the drugs may affect the brain differently depending on their duration of action.
While the potency of LSD is high compared to that of other phenethylamines, it is less potent than DOI. The 5-HT2A receptor’s affinity for LSD is lower than that for the DOI.
Related: Cross Tolerance Between LSD and Psilocybin
Dopamine D2-mediated effects in rats of psilocybin
There are various studies describing the effects of LSD and psilocychbin on the body and mind. Several researchers have demonstrated that psilocybin produces substantial and sustained reductions in anxiety and depression. For example, one study showed that psilocybin can reduce anxiety and depression in tobacco addicts.
In addition, LSD increases amplitude of BOLD signals in large regions of the brain and interacts with global signal regression (GSR) to drive changes in connectivity. Simulations indicate that these effects are largely scale invariant. Although these findings are not definitive, the results suggest that a dose-dependent relationship exists between LSD and GSR.
The effects of LSD were studied on the brain using rats trained to discriminate between the two compounds. Rats treated with LSD and psilocybin experienced full or partial substitution of their dopamine D2 receptors. In addition, these drugs significantly increased plasma levels of cortisol, PRL, oxytocin, and BDNF.
The psilocybin-induced decrease in the FC of striatum was not associated with a decrease in heart rate, as fMRI results indicate. However, the findings were not universal in rodents.
These findings are consistent with previous studies. However, at doses higher than 200 ug of LSD, the effects were not as strong and the negative effects were more pronounced. However, the effects of psilocybin were similar.
Dopamine D4 receptor involvement in VASs in rats of psilocybin
In this study, we characterized dopamine D4 receptor involvement in acute effects on rats after DOI and psilocybin administration. In DOI-trained rats, the partial D4 agonist ABT-724 produced no substitution, but had an intermediate effect on LSD-90-trained rats. Moreover, we observed that the partial D4 agonist also induced a bell-shaped dose-response curve.
In the acute effects of LSD and psocybin, dopamine D4 receptors were significantly involved in the development of an euphoric effect. This effect was most pronounced in the later temporal phase of LSD, whereas no effect was seen on DOI.
Acute effects of LSD and psioccybin were similar, although the latter produced slightly weaker subjective effects. In this study, the doses of psilocybin and LSD were administered at the same time. However, the doses were similar, and the differences were in the subjective effect and the intensity of the effect. The drugs were also found to differentially increase blood pressure and heart rate.
During the acute effects phase, the subjects were never left alone, but accompanied by an investigator for the duration of the experiment. In addition, they were sent home the next morning at 9:15am.
