Pharmacology, biochemistry, and behavior
September 1, 2016
Adam L Halberstadt, James Hyun, Michael A Ruderman et al.
N-allylnormetazocine (NANM) disrupts prepulse inhibition (PPI) of acoustic startle in mice, a measure of sensorimotor gating. Racemic NANM and its (+)-isomer produced dose-dependent PPI disruption (3-30 mg/kg), while the (-)-isomer had no effect. Blocking kappa opioid or sigma-1 receptors did not prevent this disruption, and a selective kappa agonist also had no effect on PPI. The findings indicate that NANM's effects on sensorimotor gating are mediated through the PCP site of the NMDA receptor, not through kappa or sigma-1 receptors, consistent with evidence that sigma-1 receptors are not linked to hallucinogenic or psychotomimetic effects.
Pharmacology, biochemistry, and behavior
October 1, 2006
Richard A Glennon, Tatiana Bondareva, Richard Young
The drug of abuse alpha-ethyltryptamine (alpha-ET) produces a complex internal cue in rats. Male Sprague-Dawley rats were trained to discriminate 2.5 mg/kg alpha-ET from saline. The cue began within 30 minutes and lasted at least 4 hours. When tested with other drugs, the alpha-ET cue fully generalized to the hallucinogen DOM and to PMMA, but only partially generalized (about 40%) to amphetamine, indicating that alpha-ET's effects are not purely stimulant-like.
Pharmacology, biochemistry, and behavior
June 1, 2006
Dimitris E Emmanouil, Z Papadopoulou-Daifoti, Philip T Hagihara et al.
Nitrous oxide (N2O) exposure in rats altered serotonin (5-HT) turnover in specific brain regions: increased turnover in the hypothalamus, decreased turnover in the frontal cortex, and no changes in the hippocampus or corpus striatum. Dopamine turnover remained unchanged. In mice, pretreatment with the 5-HT2 antagonist cinanserin, the 5-HT3 antagonist LY-278,584, or the serotonin reuptake inhibitor fluoxetine did not appreciably affect N2O-induced increases in time spent in the light compartment of a light/dark exploration test, though cinanserin significantly reduced N2O-induced increases in transitions. These results indicate that while N2O influences brain serotonin function, 5-HT2 or 5-HT3 receptors or serotonin reuptake do not mediate its anxiolytic-like behavioral effects.
Pharmacology, biochemistry, and behavior
January 1, 2001
S S Hong, R Young, R A Glennon
The optical isomers of alpha-ethyltryptamine (alpha-ET) produce distinct psychoactive effects in rats. The (-)isomer produced amphetamine-like effects, while the (+)isomer produced hallucinogen-like effects. Both isomers produced effects similar to MDMA and PMMA at comparable doses. The findings suggest that alpha-ET's stimulant character resides primarily with its (-)isomer and its hallucinogenic character with the (+)enantiomer.
Pharmacology, biochemistry, and behavior
March 1, 2000
Z A Martinez, N D Halim, J L Oostwegel et al.
NMDA antagonists and dopamine agonists produce behavioral and neuropathological changes in rats that may model schizophrenia symptoms. In adult rats, both drug types disrupt sensorimotor gating measured by prepulse inhibition (PPI), mirroring PPI deficits seen in schizophrenia patients. High doses of NMDA antagonists also cause limbic system pathology similar to schizophrenia neuropathology. In 16-day-old rat pups, both the NMDA antagonist phencyclidine (PCP) and the dopamine agonist apomorphine disrupted PPI, showing early developmental functionality of the underlying substrates. However, PCP-induced neurotoxicity was only observed in adult rats, indicating that brain mechanisms responsible for PPI disruption and neurotoxicity are dissociable across development.
Pharmacology, biochemistry, and behavior
June 1, 1996
S Yajnik, J P Zacny, C J Young et al.
A crossover, double-blind trial with eleven healthy volunteers tested whether acute drug tolerance develops to the subjective, cognitive, and psychomotor effects of subanesthetic nitrous oxide at doses of 0, 10, 20, 30, and 40%. Over a 120-minute inhalation period, there was little evidence of acute tolerance to the subjective or impairing effects at any concentration.
Pharmacology, biochemistry, and behavior
August 1, 1995
J P Zacny, S Yajnik, D Coalson et al.
In two double-blind, randomized, crossover trials, eight healthy volunteers inhaled 30% nitrous oxide in oxygen for 35 minutes and were given flumazenil 10 minutes into the inhalation. Experiment 1 tested clinical doses of flumazenil (0, 0.25, 0.5, and 1.0 mg/70 kg), while Experiment 2 tested a supraclinical dose (0 and 5.0 mg/70 kg). Nitrous oxide increased ratings of high, drunk, and tingling and impaired psychomotor performance. Only the supraclinical flumazenil dose significantly reduced the high rating; other subjective effects showed non-significant decreases. Flumazenil did not affect nitrous oxide's psychomotor effects. The findings suggest that a high flumazenil dose may partially antagonize some subjective effects of nitrous oxide.
Pharmacology, biochemistry, and behavior
November 1, 1994
J P Zacny, D W Coalson, J L Lichtor et al.
Two double-blind, randomized experiments tested whether the opioid antagonist naloxone alters the mood-altering and performance-impairing effects of nitrous oxide. In both experiments, inhaling 30% nitrous oxide increased self-reported feelings of drug effect, carefreeness, drunkenness, sedation, and being high, and it worsened psychomotor performance. Naloxone, given intravenously at doses ranging from 0.01 to 10 mg per 70 kg, had no effects on its own and did not significantly change any of nitrous oxide's effects. The authors conclude that naloxone, at doses up to 10 mg, does not appear to influence the subjective or psychomotor effects of nitrous oxide.
Pharmacology, biochemistry, and behavior
October 1, 1988
D Martin, D Lodge
A series of psychoactive phencyclidine (PCP) and sigma receptor ligands were compared for their ability to block NMDA receptors using cortical wedges and isolated frog spinal cords. Phencyclidine receptor ligands, but not sigma or kappa ligands, selectively antagonized NMDA on both preparations. Combination studies suggested that dissociative anaesthetics and sigma benzomorphans act at the same site. The relative potencies of the drugs as NMDA antagonists correlated well with their potency in PCP receptor binding studies in vitro and in PCP discrimination studies in vivo.
Pharmacology, biochemistry, and behavior
March 1, 1987
R A Glennon, M Yousif, N Naiman et al.
N-monomethylation of phenylisopropylamine derivatives does not uniformly increase amphetamine-like activity. In rats trained to discriminate amphetamine from saline, N-monomethyl derivatives of several dimethoxy and trimethoxy compounds failed to produce amphetamine-appropriate responding, but the N-monomethyl derivative of cathinone (methcathinone) did. Methcathinone was more potent than racemic cathinone or amphetamine (ED50 = 0.37 mg/kg vs. 0.71 mg/kg), induced dopamine release from rat caudate nucleus tissue, and was a more potent locomotor stimulant in mice. These results support a structural and pharmacological analogy between amphetamine/methamphetamine and cathinone/methcathinone.
Pharmacology, biochemistry, and behavior
February 1, 1986
A A Larson, E G Anderson
A single low dose of LSD potentiates the dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus in cats, whereas 5-MeODMT, ketamine, and PCP inhibit it. Tolerance develops to LSD's facilitatory effect but not to 5-MeODMT's inhibition, and ketamine's effect does not produce tachyphylaxis. The raphe-evoked DRP, traditionally thought to be serotonin-mediated, may actually involve a non-serotonergic transmitter, as tryptophan and fluoxetine do not potentiate it, and it resists blockade by serotonin-depleting agents.