The Alkaloids. Chemistry and biology
2001
Scott Helsley, R A Rabin, Jerrold C Winter
4 citations
The results of the studies described here support the hypothesis that ibogaine produces its effects via selective interactions with multiple receptors. It appears that 5-HT2A, 5-HT2C, and sigma 2 receptors are involved in mediating the stimulus effects of ibogaine. In addition, opiate receptors may also be involved. In contrast, sigma 1, PCP/MK-801, 5-HT3, and 5-HT1A receptors do not appear to...
Pharmacology, biochemistry, and behavior
2000
Jerrold C Winter, R A Filipink, D Timineri et al.
80 citations
Stimulus control was established in rats trained to discriminate either 5-methoxy-N,N-dimethyltryptamine (3 mg/kg) or (-)-2,5-dimethoxy-4-methylamphetamine (0.56 mg/kg) from saline. Tests of antagonism of stimulus control were conducted using the 5-HT1A antagonists (+/-)-pindolol and WAY-100635, and the 5-HT2 receptor antagonist pirenperone. In rats trained with 5-MeO-DMT, pindolol and...
Pharmacology, biochemistry, and behavior
October 1999
J C Winter, D J Fiorella, D M Timineri et al.
More than a quarter century has passed since the demonstration that indoleamine and phenethylamine hallucinogens can function as discriminative stimuli in the rat, and that serotonergic systems are critically involved. During that period our knowledge of the physiology, pharmacology, biochemistry, and molecular biology of serotonergic receptors has increased exponentially; with each advance it...
Pharmacology, biochemistry, and behavior
July 1, 1999
Jerrold C Winter, Scott Helsley, David Fiorella et al.
14 citations
In a previous study it was observed that fluoxetine potentiates the stimulus effects of lysergic acid diethylamide (LSD). In the present investigation, stimulus control was established in groups of rats using as training drugs the hallucinogens lysergic acid diethylamide (LSD); 0.1 mg/kg), (-)-2,5-dimethoxy-4-methylamphetamine [(-)-DOM; 0.56 mg/kg], ibogaine (10 mg/kg), and...
Progress in neuro-psychopharmacology & biological psychiatry
February 1, 1999
Scott Helsley, R A Rabin, Jerrold C Winter
9 citations
1. 5-HT3, 5-HT2C, and 5-HT1A receptor ligands were assessed in rats trained to discriminate ibogaine from water. 2. Significant ibogaine-appropriate responding was observed following treatment with the 5-HT2C agonists MK-212 (79.6%) and mCPP (76.4%). This substitution was completely antagonized by metergoline, an agent with 5-HT2C antagonist properties. However, metergoline was ineffective...
Progress in Neuro-psychopharmacology and Biological Psychiatry
May 1, 1998
Scott Helsley, David Fiorella, Richard A. Rabin et al.
30 citations
1. A series of N-substituted tryptamines was compared with a series of beta-carbolines in rats trained to discriminate LSD (0.1 mg/kg) from saline. 2. Intermediate levels of substitution were elicited by MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET produced 41.3% LSD-appropriate responding at a dose of 6.0 mg/kg but only 4 of 8 subjects completed the test session thus precluding...
European Journal of Pharmacology
March 19, 1998
Scott Helsley, R A Rabin, Jerrold C Winter
6 citations
The structural features and hallucinogenic properties shared by ibogaine and certain beta-carbolines prompted the evaluation of several representative beta-carbolines in rats trained with ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted...
Pharmacology, biochemistry, and behavior
February 1, 1998
Scott Helsley, David Fiorella, R A Rabin et al.
35 citations
In the present investigation, the ability of two known hallucinogens, lysergic acid dimethylamide (LSD) and (-)-2,5-dimethoxy-4-methyl-amphetamine (DOM), to substitute for the ibogaine-induced discriminative stimulus (10 mg/kg I.P., 60 min presession) was assessed in Fischer-344 rats. In these subjects, intermediate levels of generalization were observed to both agents (LSD, 63%; DOM, 66.4%)....
Pharmacology, biochemistry, and behavior
February 1, 1998
Scott Helsley, R A Filipink, W D Bowen et al.
16 citations
Although the mechanism of action of ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains unknown, receptor binding studies suggest that ibogaine produces its effects via interactions with multiple receptor types. In addition to serotonergic receptors, which have been studied previously with respect to ibogaine, likely candidates include opiate, sigma (sigma), and...
Pharmacology, biochemistry, and behavior
September 1, 1997
Scott Helsley, David Fiorella, R A Rabin et al.
9 citations
The effects of ibogaine were studied in 12 rats trained to perform in an 8-arm radial maze. In Phase I, the mean number of sessions to criterion and cumulative errors to criterion, as well as mean response rate, were determined for two groups of six animals in a task where only four arms were baited. Group 1 received a potentially neurotoxic dose of ibogaine (50 mg/kg IP administered twice,...
Brain Research
June 13, 1997
Scott Helsley, C A Dlugos, R J Pentney et al.
19 citations
The present investigation assessed the chronic toxicity of ibogaine on cerebellar Purkinje cells in male Fischer 344 rats. A behaviorally active dose of ibogaine (10 mg/kg, i.p.) was administered to a group of six subjects every other day for 60 days while the control group received an equivalent volume of saline (1 ml/kg). Estimates of Purkinje cell number were determined using the optical...
Life Sciences
1997
Scott Helsley, R A Rabin, Jerrold C Winter
13 citations
In the present investigation, Fischer-344 rats were trained to discriminate 10.0 mg/kg of ibogaine from water using a pretreatment time of 60 minutes. Analysis of dose response data generated an ED50 of 4.6 mg/kg. The time course of the ibogaine (10.0 mg/kg) cue was also determined. The stimulus reached a maximum level of 94% ibogaine-appropriate responding at the 60-min pretreatment time. This...
Psychopharmacology
December 1995
D Fiorella, S Helsley, R A Rabin et al.
The present study was designed to investigate the hypothesis that agonist interactions at 5-HT2C receptors mediate the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Three structural classes of compounds have been described to stimulate increases in phosphoinositide (PI) hydrolysis at the 5-HT2C receptor site: phenylpiperazines, phenylalkylamines, and indolamines. Four...
Psychopharmacology
October 1995
D Fiorella, S Helsley, D S Lorrain et al.
The present study was designed to determine the effects of p-chlorophenylalanine (PCPA) and p-chloroamphetamine (PCA) administration on (1) the levels of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in rat brain, (2) the sensitivity of LSD-trained rats to the stimulus effects of LSD, and (3) the maximal levels of 5-HT2A and 5-HT2C receptor mediated...
Neuropharmacology
October 1995
D Fiorella, S Helsley, R A Rabin et al.
The present study was designed to test the hypothesis that atypical, but not typical, antipsychotics produce a functional in vivo blockade of 5-HT2A receptors. The magnitude of functional in vivo 5-HT2A receptor blockade elicited by representative compounds from each of the six major structural classes of typical antipsychotics, and the representative atypical antipsychotics clozapine and...