Brain ResearchDecember 1, 1994P A Kelly, I M Ritchie, M Sangra et al.
Cerebral blood flow and glucose utilization were measured in rat neocortex, hippocampus and striatum following methylenedioxymethamphetamine injection (5 mg/kg, i.v.), using the tracers [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. In control rats, blood flow was coupled to glucose metabolism, but in methylenedioxymethamphetamine-treated rats, marked hyperperfusion was measured in...
Ibogaine, a naturally occurring alkaloid, has been claimed to be effective in treating addiction to opioid and stimulant drugs and has been reported to decrease morphine and cocaine self-administration in rats. The present study sought to determine if other iboga alkaloids, as well as the chemically related harmala alkaloid harmaline, would also reduce the intravenous self-administration of...
We have used female and male transgenic (Tg) mice that carry the complete sequence of the human copper-zinc (CuZn) superoxide dismutase (SOD) gene in order to assess the lethal effects of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA). In contrast to non-Tg mice, both heterozygous and homozygous SOD-Tg mice showed resistance to the lethal effects of both drugs. Females...
5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) is an indolealkylamine which has agonist activity at 5HT receptors. In the present investigation, 5-MeODMT had two types of effects on medullary respiratory neurons of the cat. Iontophoretic administration or i.v. doses (43 +/- 8.9 micrograms/kg) of 5-MeODMT hyperpolarized respiratory neurons and severely reduced action potential discharges....
Systemic administration of ibogaine (40 mg/kg, i.p.) has been reported to induce both acute (1-3 h) and persistent (19-20 h) changes in extracellular levels of dopamine and its metabolites in the nucleus accumbens and striatum. In the present study, local administration of ibogaine to the striatum and nucleus accumbens produced effects that mimicked both the acute and persistent effects of...
The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) in rat brain was attenuated significantly by coadministration of several benzylpiperazines (p-nitrobenzylpiperazine, p-chlorobenzylpiperazine and 1-piperonylpiperazine), which were weak inhibitors for [3H]6-nitroquipazine binding to the 5-hydroxytryptamine (5-HT) transporter in rat brain. These results suggest that these...
Previous studies in rats have shown that ibogaine inhibits neurochemical and behavioral effects of morphine yet potentiates similar effects of (+)-amphetamine. To assess whether these different functional interactions have a metabolic basis, brain levels of morphine and (+)-amphetamine were measured by gas chromatography-mass spectrometry after ibogaine pretreatment (19 h before injection of...
Ibogaine, an indolalkylamine, has been proposed for use in treating stimulant addiction. In the present study we sought to determine if ibogaine had any effects on the neurochemical and motor changes induced by D-amphetamine that would substantiate the anti-addictive claim. Ibogaine (40 mg/kg, i.p.) injected 19 h prior to a D-amphetamine challenge (1.25 mg/kg, i.p.) potentiated the expected...
Ibogaine, an indolalkylamine, proposed for use in treating opiate and stimulant addiction, has been shown to modulate the dopaminergic system acutely and one day later. In the present study we sought to systematically determine the effects of ibogaine on the levels of dopamine (DA) and the dopamine metabolites 3,4 dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in tissue at...
Assays using radioligands were used to assess the actions of ibogaine and harmaline on various receptor types. Ibogaine congeners showed affinity for opiate receptors whereas harmaline and harmine did not. The Ki for coronaridine was 2.0 microM at mu-opiate receptors. The Kis for coronaridine and tabernanthine at the delta-opiate receptors were 8.1 and 3.1 microM, respectively. Ibogaine,...
Methylenedioxymethamphetamine (MDMA) produced a significant hyperthermia in rats which was antagonized in a competitive manner by the selective 5-HT2 antagonist, MDL 11,939. The 5-HT antagonist also blocked MDMA-induced neurotoxicity as assessed by the decline in regional 5-HT concentrations observed 1 week later. These two effects of MDL 11,939 were dissociated at higher doses of MDMA where...
Animal studies have established a correlation between release of 5-hydroxytryptamine (5-HT) and the long-term reduction of 5-HT (toxicity) by 3,4-methylenedioxymethamphetamine (MDMA) with the S(+) enantiomer being more active than the R(-). Using a microculture system of fetal raphe neurons, the enantiomers of MDMA were tested to determine if a similar difference in potency existed. The results...
This study examined whether 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) could be used to detect serotonergic damage induced by (+/-)-3,4-methylenedioxymethamphetamine (MDMA) in the central nervous system (CNS) of non-human primates. Monkeys were administered toxic doses of MDMA; two weeks later, the animals were lightly anesthetized with ether and CSF was obtained by means...
This study compared the toxic effects of oral versus subcutaneous and single versus multiple doses of 3,4-methylenedioxymethamphetamine (MDMA) on central serotonergic neurons in non-human primates. Orally administered MDMA was approximately one-half as effective as subcutaneously administered drug. Multiple doses were more effective than single doses, but a single 5 mg/kg dose of MDMA given...
Brain ResearchDecember 1, 1987A D Weissman, M Dam, E D London
The effects of phencyclidine (PCP; 0.5, 1,5, 10 mg/kg, i.v.) on local cerebral glucose utilization (LCGU) in the rat were studied with the 2-deoxy-D-[1-14C]glucose method. Significant findings were obtained in 41 of 87 brain regions of PCP-treated rats (25-270% of control). Rates of LCGU increased throughout the limbic system, except the habenula. Although LCGU increased in most sensory...
As previously reported, systemic administration of the hallucinogens D-lysergic acid diethylamide (LSD) (5-10 micrograms/kg) and mescaline (2 mg/kg) in the anesthetized rat produced a decrease in spontaneous activity but, paradoxically, facilitated activation of locus coeruleus (LC) neurons by sciatic nerve stimulation. In the present study, the hallucinogen 2,5-dimethoxy-4-methylamphetamine...
The acute effects of the 5-hydroxytryptamine agonist, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. Noradrenaline depletion, following the systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 2 X 50 mg/kg,...
Brain ResearchFebruary 11, 1985R Lalonde, M I Botez1 citation
Male Sprague-Dawley rats were injected with phenytoin (PHT) once a day for 20 consecutive days and then tested as to their response to 5-methoxy-N,N-dimethyltryptamine (5-MDMT), a 5-hydroxytryptamine (5-HT) agonist, at 1 and 3 mg/kg on days 21 and 28. It was found that long-term PHT administration decreased the intensity of a stereotyped motor response induced by 5-MDMT (3 mg/kg) on day 21 but...
Analgesia induced by footshock (2 mA, 30 s) is decreased by the 5-HT releaser, fenfluramine, and the rapidly acting 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). These decreases are blocked by the 5-HT antagonists, cyproheptadine and methiothepin. However, the antagonists when given alone do not influence shock-induced analgesia. Therefore, analgesia induced by brief footshock in...
5-Methoxy-N,N-dimethyltryptamine (5-MeODMT), a potent serotonin (5-HT) receptor agonist, exerts a biphasic effect on rat prolactin (PRL) secretion. 5-MeODMT (2.5-10 mg/kg) produces a marked, dose-related but short-lasting (less than 30 min) rise in serum PRL levels. At intervals longer than 30 min, 5-MeODMT (1-15 mg/kg) inhibits the stimulation of PRL secretion by another 5-HT agonist,...
Brain ResearchNovember 4, 1982M A McCall, D G Tieman, H V Hirsch
In kittens, but not in adult cats, depriving one eye of pattern vision by suturing the lids shut (monocular deprivation or MD) for one week reduces the proportion of binocular units in the visual cortex. A sensitivity of cortical units in adult cats to MD can be produced by infusing exogenous monoamines into the visual cortex. Since LSD interacts with monoamines, we have examined the effects of...
The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of several hallucinogenic drugs while concurrently monitoring the activity of raphe neurons in freely moving cats. LSD produced a dose-dependent decrease in raphe unit activity and a dose-dependent increase in...
The influence of D-lysergic acid diethylamide (LSD) and mescaline on adenylate cyclase activity was studied in homogenates of Cebus and rhesus monkey anterior limbic cortex (ALC), frontal cortex (FC), caudate nucleus and retina. Previous studies have shown these tissues to contain dopamine-stimulated adenylate cyclase (AC). In addition, we are now reporting the presence of a dopamine-sensitive...
In the course of examining the complete dose-response relationship for the behavioral effects of LSD in the cat, we discovered that, in addition to large increases in investigatory and hallucinatory-like responses, two behaviors, not previously reported, are emitted with a high probability under LSD. Beginning from a baseline of essentially zero in saline-treated animals, limb flicks and...
D-[3H]LSD binds saturably, reversibly, and with a high affinity (KD = 10 nM) to rat brain membranes. The association and dissociation rates of binding are temperature dependent and fastest at 37 degrees C. Binding is enriched in crude microsomal (P3) membranes. D-[3H]LSD binding is stereospecific as L-LSD, the psychotropically inactive enatiomer, is 1000 times weaker than D-LSD as a displacing...