100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug.
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Animals↗
Biomedical subjects
P Popik
Publications and source records attributed to P Popik.
Adenosine A3 receptor stimulation and cerebral ischemia.
Chronic treatment with the selective adenosine A3 receptor agonist N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (IB-MECA) administered prior to either 10 or 20 min forebrain ischemia in gerbils resulted in improved postischemic cerebral blood circulation, survival, and neuronal preservation. Opposite effects, i.e., impaired postischemic blood flow, enhanced mortality, and extensive neuronal destruction in the hippocampus were seen when IB-MECA was given acutely. Neither adenosine A1 nor A2 receptors are involved in these actions. The data indicate that stimulation of adenosine A3 receptors may play an important role in the development of ischemic damage, and that adenosine A3 receptors may offer a new target for therapeutic interventions.
Adenosine↗
The effect of electroconvulsive shock and nifedipine on spatial learning and memory in rats.
Several traumatic events including brain contusion, electroconvulsive shock therapy, epileptic seizures and others, may cause short-term retrograde amnesia. In spite of much recent attention, pharmacological treatment of memory impairment has not been fully successful. In the present paper we report on the possible antiamnesic action of the L-type calcium channel blocker, nifedipine. Rats trained in the spatial memory task showed gradual improvement in the escape latency to find the submerged platform. After completion of the learning, they also showed a strong spatial bias toward the place that previously contained the target platform. Prolonged post-trial electroconvulsive shock induced memory impairment. The calcium channel blocker, previously reported as a "cognitive enhancer," given either before or after the learning trial revealed no antiamnesic effect. Nifedipine also does not exert any action when given alone. These results suggest that the drug may not have antiamnesic action on human memory disturbed by electroconvulsive therapy.
Animals↗
The putative anti-addictive drug ibogaine is a competitive inhibitor of [3H]MK-801 binding to the NMDA receptor complex.
Ibogaine is a putative anti-addictive drug with potential efficacy for the treatment of opiate, stimulant, and alcohol abuse. We now report ibogaine is a competitive inhibitor (Ki, 1.01 +/- 0.1 microM) of [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptor coupled cation channels. Since MK-801 can attenuate the development of tolerance to morphine and alcohol as well as sensitization to stimulants in preclinical studies, the reported ability of ibogaine to modify drug-seeking behavior in man may be attributable to a blockade of NMDA receptor coupled cation channels.
Animals↗
Retrieval associated cholinergic activity and its inhibition by memory updating.
Both hippocampal cholinergic and glutamatergic systems are believed to be engaged in learning and memory. By measuring behavior and ex vivo second messenger inositol phosphate (IP) accumulation, we investigated biochemical responses of cholinergic receptors to retrieval and acquisition processes in rats trained in a spatial task. We report that in rats retrieving spatial information, carbachol--induced IP accumulation strongly and transiently increased above values observed in handled controls and rats acquiring new information, and that this increase was profoundly inhibited by N-methyl-D-aspartate (NMDA). These results suggest that memory retrieval, rather than formation of a memory trace, is related to increased responsiveness of the hippocampal cholinergic system, and that formation of a new memory trace, which updates long-term memory, inhibits this cholinergic activation, possibly by a learning-associated increase in NMDA receptor activation. Moreover, the present study shows that the distinction between acquisition and retrieval processes can be demonstrated on both a behavioral and biochemical level.
Analysis of Variance↗
Adaptation of the N-methyl-D-aspartate receptor complex following chronic antidepressant treatments.
Chronic (14 day) but not acute (1 day) treatment of mice with clinically active antidepressants produces a significant (approximately 1.8-4.3 fold) reduction in the potency of glycine to inhibit [3H]-5,7-dichlorkynurenic acid (5,7-DCKA) binding to strychnine-insensitive glycine receptors in neocortical membranes. Moreover, these effects were not observed following chronic treatment with a variety of nonantidepressant drugs such as D-deprenyl, chlorpromazine, salbutamol, scopolamine and chlordiazepoxide. The time course and dose-response relationships for this effect were examined after treatment with two representative antidepressant drugs (imipramine and citalopram) and electriconvulsive shock (ECS). Increases in the IC50 of glycine to inhibit [3H]-5,7-DCKA binding were observed after treatment for 7 days with ECS, 10 days with citalopram and 14 days with imipramine, respectively, and were no longer apparent by the 10th day after cessation of treatment. These findings indicate that the antidepressant-induced reduction in the IC50 of glycine to inhibit [3H]-5,7-DCKA binding is: 1) a slowly developing, adaptive phenomenon; 2) remarkably persistent after cessation of treatment; and 3) a significantly better predictor of antidepressant activity (22 of 23 drugs) than either beta adrenoceptor down-regulation (15 of 23 drugs) or efficacy in the forced swim test (13 of 23 drugs) [P < .01 vs. each measure, Fisher's Exact Test]. The ability of antidepressants drawn from every principal therapeutic class to effect adaptive changes in the N-methyl-D-aspartate receptor complex is consistent with the hypothesis that this ligand-gated ion channel serves as a final common pathway of antidepressant action and indicates that glutamatergic pathways may be involved in the pathophysiology of depression.
Adaptation, Physiological↗
Ca2+ antagonists effect an antidepressant-like adaptation of the NMDA receptor complex.
Chronic, but not acute treatment of mice with nimodipine and diltiazem produce significant increases in the IC50 of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding in cerebral cortex. Such adaptive changes in the ligand binding properties of the NMDA receptor complex are also manifested following chronic treatment with antidepressants from every principal therapeutic class. These findings indicate voltage-dependent calcium channel antagonists would be strong candidates for rigorous clinical trials in depressive disorders.
Animals↗
Social transmission of flavored tea preferences: facilitation by a vasopressin analog and oxytocin.
Social transmission of information was tested in a procedure in which a rat (Observer) could demonstrate preference for a flavored tea as drinking solution that a con-specific (Demonstrator) had consumed just prior to a period of social interaction between the two animals. The cue in this procedure, probably olfactory in nature, was remembered for a relatively short period of time. It was prolonged when the Observers were treated with dresglycinamide[Arg8]-vasopressin (DGAVP) or oxytocin immediately after the encounter with the Demonstrator. DGAVP was effective after the injection of 15 micrograms.kg-1 but not of 1.5 ng.kg-1. Oxytocin induced the effect in doses ranging from 1.5 ng.kg-1 to 15 micrograms.kg-1. A dose of 0.15 ng.kg-1 was inactive. The influence of the peptides was cue specific. It is concluded that DGAVP and oxytocin facilitate social transmission of information, as previously found for social recognition.
Animals↗
Low doses of oxytocin facilitate social recognition in rats.
Social recognition of juveniles by adult male residents has been shown to be modulated by neurohypophyseal hormones. The decrease of social investigation behavior during a second encounter with the same juvenile serves as index for social recognition. In the present study it was found that low doses (0.09-6.0 ng.kg-1) of oxytocin (OXT) given subcutaneously dose dependently facilitated social recognition. The effect of OXT appeared specific, since no change in social investigation was found when a novel juvenile was tested during the second encounter. No disturbances of social recognition by the low doses of OXT could be detected, in contrast to higher doses of this hormone. Other neurohypophyseal hormones, vasopressin and vasotocin, did not facilitate social recognition when tested in the same range of low doses.
Animals↗
Long-term facilitation of social recognition in rats by vasopressin related peptides: a structure-activity study.
The effect of several vasopressin-related peptides was investigated in the social recognition paradigm, that consists of two successive encounters of a resident and a juvenile rat. The decrease of social investigation time of the resident rat during the second encounter served as a measure for social recognition. Single administration (3.0 micrograms, s.c.) of the vasopressin (AVP)-related peptides AVP-(1-8), AVP-(1-7) or AVP-(1-6), injected just after the first encounter, resulted in social recognition after 24 hours. Such an effect was not observed after placebo treatment or an injection with AVP-(1-5), [pGlu4, Cyt6]AVP-(4-8), [pGlu4, Cyt6]-AVP-(4-9), AVP-(7-9) or oxytocin-(1-6)-NH2. The peptide AVP-(1-6) was also active when administered in a dose of 0.3 micrograms in contrast to other peptides. Thus, vasopressin related peptides induce long term facilitation of social recognition and this action resides in the covalent ring structure of vasopressin. This effect resembles the vasopressin-induced facilitation of particular memory processes, as revealed with other behavioral paradigms.
Amino Acid Sequence↗
Neuropeptides related to [Arg8]vasopressin facilitates social recognition in rats.
The decrease of social investigations of adult rats during a second encounter session with the same juvenile was used as an index of social recognition or memory. Social recognition was present when the interexposure interval was 15 or 30 min, but not when this interval lasted 60 or 120 min. Animals treated with desglycinamide[Arg8]vasopressin (DGAVP) (6.0 micrograms.kg-1, SC) or [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8] (1.0 microgram.kg-1, SC), immediately after the first encounter, recognized the same juveniles still after 120 min, suggesting a facilitatory effect of these peptides on social recognition and that this effect of vasopressin is dissociated from the classical endocrine effects of this hormone. The decrease of social investigating behavior, in both placebo- and DGAVP-treated rats, was completely due to a decrease in anogenital exploration, indicating that the social recognition in rats is presumably based on odor cues from the anogenital part of the body.
Animals↗
Opposite action of oxytocin and its peptide antagonists on social memory in rats.
The synthetic 1-beta,beta-disubstituted analogues of [1-deamino]-oxytocin, [1'-(1'-thio-4'-methylcyclohexane)-acetic acid 1]-oxytocin (MeCAOT) a peripheral oxytocin antagonist, and [1'-(1'-methyl-4'-thiopiperidine)-acetic acid 1]-oxytocin (MePAOT), devoid of peripheral anti-oxytocin activity, were found to improve social memory of rats. The social memory in rats was disrupted by a wide range of doses of oxytocin (6-750 mU/kg) and this amnestic effect of oxytocin was antagonised by MePAOT and MeCAOT.
Animals↗
Oxytocin but not vasopressin facilitates social recognition following injection into the medial preoptic area of the rat brain.
Social recognition of juvenile rats by adult male residents has been shown to be modulated by peripheral administration of neurohypophyseal hormones vasopressin and oxytocin. In the present study, the effects of these peptides on social recognition were investigated after local injection into the medial preoptic area of the hypothalamus. It was found that oxytocin given in a wide range of doses (0.3-1000 pg) facilitated social recognition. This effect was not blocked by pretreatment with oxytocin receptor antagonist desGly(NH2)9-d(CH2)5[Tyr(Me)2Thr4]OVT. Oxytocin injected into the septum in doses of 0.03-3 pg was not effective. Administration of vasopressin (100 or 1000 pg), [pGlu4,Cyt6]AVP-(4-8) (200 pg) or [pGlu4,Cyt6]AVP-(4-9) (200 pg) into the medial preoptic area did not influence social recognition. It is concluded that the medial preoptic area is a sensitive brain site for the oxytocin-induced facilitation of social recognition in rats.
Angiotensin Receptor Antagonists↗
Recognition cue in the rat's social memory paradigm.
The cue used by an adult resident rat for recognition of a just met juvenile in the social memory paradigm was assessed by manipulating the amount of olfactory information and enhancing the recognition with arginine8-vasopressin (AVP). Social recognition was impaired in anosmic resident rats, suggesting that the recognition cue is olfactory in nature. Washed juveniles were recognized by AVP but not placebo treated residents, independently of whether after washing they were marked with previously collected urine of the residents or not. Preputialectomized juveniles were recognized neither by placebo nor by AVP treated residents. The results suggest that the scents originating from the preputial gland of the juvenile serve as the recognition cue in the social memory paradigm of rats.
Animals↗
Clinically available NMDA antagonist, memantine, attenuates tolerance to analgesic effects of morphine in a mouse tail flick test.
Converging lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptor antagonists attenuate the development of morphine tolerance tested in antinociception assays in rodents. The present study extends these findings to the effects of clinically available NMDA receptor antagonist, memantine. Male Albino Swiss mice were tested for analgesia using the tail-flick apparatus. Preliminary experiment was designed to find out the optimal dose of morphine and the number of injections that would produce tolerance to its analgesic effects. In the main experiment, during the development of tolerance period (6 days), mice received 10 mg/kg sc b.i.d. morphine injections in the animal room (non-associative tolerance). This treatment resulted in 5.8 fold rightward shift of morphine cumulative dose-response effect from 3.39 mg/kg on day 1 to 16.19 mg/kg on day 8 of the experiment. Memantine pretreatment (5 and 10 mg/kg, but not 2.5 mg/kg), given 30 min prior to each morphine dose during the development of tolerance period, inhibited the rightward shift of morphine cumulative dose-response curve. Thus, pretreatment with memantine at doses of 2.5, 5 and 10 mg/kg resulted in ED50 values of 12.13, 4.74 and 1.95 mg/kg, respectively, corresponding to 3.35, 1.02 and 0.94 fold changes. These data indicate that low affinity, clinically available NMDA receptor antagonist, memantine, may be used to inhibit the development of morphine tolerance.
Analgesics, Opioid↗
Colostrinin and colostrinin-derived nonapeptide (colostral-val nonapeptide, CVNP) facilitate learning and memory in rats.
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Animals↗
Strain differences in changes in some parameters of cerebral cortical adrenergic system following chronic imipramine administration to rats.
The characteristics of [3H]prazosin binding sites in the membranes from cerebral cortex, the basal level of formation of cyclic AMP in cortical slices, and the responsiveness of the cyclic AMP generating system to noradrenaline and isoproterenol in this preparation were measured in Long-Evans, Wistar and Sprague-Dawley rats treated chronically with saline or imipramine. No differences between strains and treatments were observed regarding the Bmax and KD of [3H]prazosin binding sites. The basal levels of cyclic AMP formation were similar in control rats of all strains, but imipramine treatment augmented it significantly in Sprague-Dawley rats. The responses of the cyclic AMP generating system to noradrenaline were significantly lower in Long-Evans than in the remaining strains of rats. Only in Sprague-Dawley rats a significant downregulation of response to noradrenaline was observed after imipramine treatment. All three strains of rats differed significantly among themselves in their responsiveness to isoproterenol; only in Sprague-Dawley rats this response was down-regulated significantly (by 80%) by imipramine treatment.
Animals↗
Stability and variability of locomotor responses of laboratory rodents. II. Native exploratory and basal locomotor activity of Wistar rats.
The exploratory and basal locomotor activities were tested in four groups of Wistar rats twice, at a 4 day interval, to investigate the variability of responses and their changes on repetition of the test. The locomotor activity of rats was much lower than that of mice, particularly when the basal locomotor activity is concerned, but the individual variability was much higher. The exploratory activity declined significantly on the repeated testing. However, there was a good correlation between the individual exploratory activity in two consecutive tests, which suggests that preselection in the rat may be useful.
Animals↗