The effects of dizocilpine and buprenorphine pretreatment on behavior reinforced by orally delivered phencyclidine (PCP) and saccharin, and on PCP withdrawal-induced disruptions in food-maintained responding were examined. Sixteen male rhesus monkeys were used in six different experimental protocols. Two groups of monkeys (N = 4-5) self-administered PCP (0.25 mg/ml) and water under concurrent...
Fifteen beta-carboline derivatives, including those found in the South American hallucinogenic plant Banisteriopsis caapi, were injected IP and IVC into mice. Subsequent behavioral changes were observed and the levels of the compounds in brain tissue were determined. It was found that following IP administration, tremors and/or convulsions were induced by beta-carbolines having aliphatic alkyl...
Isopropyl (IPLA), N-methyl-N-isopropyl (MIPLA), N-ethyl-N-isopropyl (EIPLA), and N,N-diisopropyl (DIPLA) lysergamides were evaluated for lysergic acid diethylamide (LSD)-like activity. In rats trained to discriminate 0.08 mg/kg LSD tartrate from saline, each of the subject compounds completely substituted, with an ED50 two to three times larger than that of LSD except for DIPLA, which had an...
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...
A series of experiments examined the role of dopamine in the conditioned taste aversion (CTA) produced by 3,4-methylenedioxymethamphetamine (MDMA) and d-amphetamine in rats. The CTA induced by MDMA (1.0 mg/kg) was unaffected by the D1 dopamine receptor antagonist SCH23390 (0.3 or 0.6 mg/kg), the D2 receptor antagonist raclopride (0.3 or 0.6 mg/kg), SCH23390 and raclopride combined (both 0.3 or...
After a period of forced exposure to 300 mg/l cocaine HCl in drinking water for a period of one week, followed by forced exposure to 200 mg/l cocaine for an additional week, male C57BL/6By mice developed a preference for cocaine when given a choice of drinking either water or a solution containing cocaine (200 mg/l). The mean daily intake of cocaine during the choice period was 26 +/- 1 mg/kg...
The cannabimimetic activity of the two enantiomers of 11-hydroxy-delta-8-tetrahydrocannabinol (11-OH-delta-8-THC) was evaluated in pigeons trained to discriminate between the presence and absence of (-)-delta-9-tetrahydrocannabinol [(-)-delta-9-THC]. (-)-11-OH-Delta-8-THC exhibited cannabimimetic activity with a potency (ED50, 0.17 mg/kg) similar to that of delta-9-THC. The duration of action...
The reinforcing, subjective, and psychomotor effects of 30 min of inhalation of 20% nitrous oxide were determined in 12 healthy volunteers using a choice paradigm with 100% oxygen as placebo. Nitrous oxide was chosen on only 22% of choice occasions, indicating that, in general, this concentration did not function as a reinforcer. Nitrous oxide produced changes in mood, but had no effect on...
Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the substantia nigra pars reticulata (SNr) of awake rats was shown to influence oral behavior. The 5-HT1A agonist (R)-8-hydroxy-2-(di-propylamino)- tetralin (8-OH-DPAT) (1.3-13 nmol on each side) produced a dose-dependent depression of vacuous chewing movements (VCMs) that lasted about 20 min. The (R)-8-OH-DPAT-induced depression of...
One-carbon homologation of phenylalkylamine or indolylalkylamine hallucinogens containing an alpha-methyl substituent typically results in a reduction of hallucinogenic potency; however, this same structural change has little to no effect on agents that produce MDMA-like effects. In the present investigation, rats trained to discriminate 1.5 mg/kg of MDMA (3,4-methylenedioxymethamphetamine)...
Many drugs of abuse such as d-amphetamine support the development of taste aversion in a conditioned taste aversion paradigm. However, it has yet to be established whether methylenedioxymethamphetamine (MDMA), an amphetamine-like stimulant, has this property. A direct comparison was made between MDMA and d-amphetamine over a dose range of 0.125-2.0 mg/kg (SC). Two pairings of either drug with...
The effect of acute, reversible depletion of either serotonin [5-hydroxytryptamine (5-HT)] or dopamine (DA) on the long-term (7-day) decrease of brain 5-HT content produced after 3,4-methylenedioxymethamphetamine (MDMA) administration was investigated. The tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (alpha-MPT) significantly attenuated the acute increase in DA efflux produced by MDMA...
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...
The stimulus effects of ibogaine were compared with those of yohimbine, an alpha 2-adrenoceptor antagonist, 2,5-dimethoxy-4-methylamphetamine (DOM), a 5-hydroxytryptamine2 (5-HT2) agonist, and lysergic acid diethylamide (LSD), a nonspecific 5-HT agonist. Rats were trained with either yohimbine (6 mg/kg), DOM (0.6 mg/kg), or LSD (0.1 mg/kg) vs. no treatment in a two-lever discrimination task....
Using a standard two-lever operant paradigm, male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg N-methyl-1(3,4-methylenedioxyphenyl)-2- aminopropane (MDMA) from saline using a variable-interval 15-s schedule of reinforcement for food reward. Tests of stimulus antagonism were conducted to further define the mechanism of action of MDMA as a discriminative stimulus. Low doses of the...
A double-blind, placebo-controlled study assessed acute effects on human cognition of marijuana smoking involving long or short durations of inhalation and breath holding. During eight test sessions, 48 adult, male volunteers completed standardized, pencil-and-paper tests of educational development and ability, as well as computerized tests of learning, associative processes, abstraction, and...
To determine whether metabolite-related analogs of N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) produce stimulus effects similar to those of the parent compound, and to determine the structural requirements associated with the MDMA stimulus, several MDMA analogs were examined in tests of stimulus generalization using rats trained to discriminate 1.5 mg/kg MDMA from saline....
Alcohol preference and manifestation of alcoholism are thought by many to be associated with serotonin (5-HT) dysfunction in the brain. Thus, experiments were performed to determine the effect of acute and subchronic administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analog that stimulates 5-HT release, on alcohol preference in two strains of alcohol-preferring...
The acute and chronic effects of cocaine were evaluated on the 5-hydroxytryptamine (5-HT)-receptor 5-HT2 mediated behavioral function, the head-twitch response (HTR), in mice. In a recent study, we reported that the (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)-induced HTR was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-HT1A and adrenergic...
The present investigations sought to determine the effects of 3,4-methylenedioxyamphetamine (MDA) on: 1) differential conditioning of the rabbit's nictitating membrane response to the serial compounds A-X-US (tone-light-reinforced compound) and B-X (white noise-light-unreinforced compound) by examining differential responding to A and B and their conditional control over responding to X within...
Measurements of binocular depth inversion using a stereoscopic slide projection with polarized light were performed in healthy volunteers before and after cannabis intake. Since binocular depth inversion represents an illusion occurring in the perception of semantically meaningful objects projected in a 3-D inverted fashion, the hypothesis can be tested that cannabis-induced "psychedelic...
Several laboratories have reported that chronic exposure to delta-9-tetrahydrocannabinol (THC) or marijuana extracts persistently altered the structure and function of the rat hippocampus, a paleocortical brain region involved with learning and memory processes in both rats and humans. Certain choices must be made in designing experiments to evaluate cannabis neurotoxicity, such as dose, route...
THC is the major psychoactive constituent of marijuana and is known to produce psychopharmacological effects in humans. These studies were designed to determine whether acute or chronic exposure to marijuana smoke or THC produces in vitro or in vivo neurochemical alterations in rat or monkey brain. For the in vitro study, THC was added (1-100 nM) to membranes prepared from different regions of...
This study entailed the adoption of a well-established behavioral paradigm, spontaneous alternation, as a possible animal model for some of the symptoms observed in obsessive-compulsive disorder (OCD) in humans. Food-deprived rats were run in a T-maze in which both a black and a white goal box were equally baited with a small amount of chocolate milk. Each rat was given 7 trials every other day...
Methylenedioxymethamphetamine (MDMA) can produce a conditioned place preference (CPP) among rats. The ability of MDMA to produce a CPP was assessed while some rats were under the influence of naltrexone, 56 mg/kg, given 4 h before conditioning. Naltrexone attenuated MDMA's ability to produce a CPP without completely blocking MDMA's effects. Having noticed previously the production of seminal...