The phenethylamine and indoleamine classes of hallucinogens demonstrate distinct pharmacological properties, although they share a serotonin(2A) (5-HT(2A)) receptor mechanism of action (MOA). The 5-HT(2A) receptor signals through phosphatidylinositol (PI) hydrolysis, which is initiated upon activation of phospholipase C (PLC). The role of PI hydrolysis in the effects of hallucinogens remains...
RationaleAfter decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however.ObjectivesTwo commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and...
Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims...
Associative learning during Pavlovian eyeblink conditioning has been shown to be regulated by 5-HT2A receptors. The existence of inverse agonists that retard learning through an action at the 5-HT2A receptor suggests the existence of constitutive activity at that receptor and that depletion of serotonin should have minimal effects on learning. We examined whether depletion of serotonin would...
This study examined the effects of the hallucinogen, MDA, on brain content of monoamines and their metabolites in the rabbit. A single 1.8 mg/kg dose of MDA produced 30 to 64% increases in the 5-HT content of frontal cortex from 30 to 120 min after injection and a decrease in 5-HT turnover from 30 min to 8 h, but had no effect in hippocampus, caudate nucleus, or hypothalamus. A single 3.6 mg/kg...
The rate of associative learning was assessed in the presence of saline versus methylenedioxymethamphetamine (MDMA) at doses of 0.95, 1.9, and 3.8 mg/kg. The conditioned stimuli (CSs) were lights and tones and the unconditioned stimulus (US) was a corneal air puff. Learning was enhanced by all but the highest dose of drug tested, and the enhancement was most pronounced when light was used as...
The behavioral effects of a single, acute dose of methylenedioxyamphetamine (MDA) were assessed using the rabbit nictitating membrane (NM) preparation. Acquisition of the classically conditioned NM response was carried out in a single session under MDA at doses of 10 and 20 mumol/kg (1.79 and 3.58 mg/kg, respectively) and retention was assessed during a drug-free state 48 h later. In agreement...
Three experiments were conducted to determine the effects of LSD (30 nmol/kg) on the acquisition of the rabbit's classically conditioned nictitating membrane response. Experiment 1 revealed that LSD significantly enhanced the acquisition of conditioned responses [CRs], and control groups receiving unpaired conditioned stimulus/unconditioned stimulus (CS/UCS) presentations served to identify...