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Biomedical subjects

W E Fantegrossi

Publications and source records attributed to W E Fantegrossi.

7 recordsLinked to original sources
PubMed2006

Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats.

Few studies have examined the effects of 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) in vivo. In these studies, 5-MeO-DIPT was tested in a drug-elicited head twitch assay in mice where it was compared to the structurally similar hallucinogen N,N-dimethyltryptamine (N,N-DMT) and challenged with the selective serotonin (5-HT)2A antagonist M100907, and in a lysergic acid diethylamide (LSD) discrimination assay in rats where its subjective effects were challenged with M100907 or the 5-HT 1A selective antagonist WAY-100635. Finally, the affinity of 5-MeO-DIPT for three distinct 5-HT receptors was determined in rat brain. 5-MeO-DIPT, but not N,N-DMT, induced the head twitch responses in the mouse, and this effect was potently antagonized by prior administration of M100907. In rats trained with LSD as a discriminative stimulus, there was an intermediate degree (75%) of generalization to 5-MeO-DIPT and a dose-dependent suppression of response rates. These interoceptive effects were abolished by M100907, but were not significantly attenuated by WAY-100635. Finally, 5-MeO-DIPT had micromolar affinity for 5-HT 2A and 5-HT 2C receptors, but much higher affinity for 5-HT 1A receptors. 5-MeO-DIPT is thus effective in two rodent models of 5-HT2 agonist activity, and has affinity at receptors relevant to hallucinogen effects. The effectiveness with which M100907 antagonizes the behavioral actions of this compound, coupled with the lack of significant antagonist effects of WAY-100635, strongly suggests that the 5-HT 2A receptor is an important site of action for 5-MeO-DIPT, despite its apparent in vitro selectivity for the 5-HT 1A receptor.

5-Methoxytryptamine↗
PubMed2005

Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys.

1-Benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are two designer drugs that are often sold in combination tablets via the internet. The discriminative stimulus properties and reinforcing effects of these compounds have not previously been assessed in laboratory primates. In this regard, the reinforcing effects of BZP and TFMPP (alone, and in combination) were assessed via intravenous self-administration in rhesus monkeys previously trained to self-administer cocaine, while the discriminative stimulus effects of these compounds were determined in rhesus monkeys trained to discriminate amphetamine (AMPH) from saline. BZP was an effective reinforcer in self-administration tests, and appeared to induce long-lasting direct effects on behavior following sessions where BZP intakes were large. Additionally, BZP occasioned AMPH-appropriate responding in a dose-dependent manner, and produced full generalization in all monkeys tested. In contrast, TFMPP was not self-administered by any subjects and occasioned essentially no AMPH-appropriate responding at any dose tested. Non-contingent TFMPP administration had direct effects on behavior and abolished subsequent cocaine-maintained responding. Similarly, self-administration of various ratios of BZP:TFMPP combinations engendered less responding than did BZP alone. The present results suggest that BZP has abuse liability of the amphetamine type, but that such effects are not shared by TFMPP.

Animals↗
PubMed2004

Antinociceptive, hypothermic, hypotensive, and reinforcing effects of a novel neurotensin receptor agonist, NT69L, in rhesus monkeys.

Neurotensin (NT) is a tridecapeptide found in the nervous system, as well as elsewhere in the body. It has anatomic and functional relationships to dopaminergic neurons in brain. NT has been implicated in the actions of antipsychotic drugs and psychostimulants, and animal studies suggest that neurotensin directly injected into brain has reinforcing effects. Previously, we showed that one of our brain-penetrating analogs of neurotensin, NT69L (N-methyl-L-Arg, L-Lys, L-Pro, L-neo-Trp, L-tert-Leu, L-Leu), has many pharmacological effects in rats including antinociception, hypothermia, and blockade of the hyperactivity caused by psychostimulants (cocaine, D-amphetamine, and nicotine). Since these studies in rats suggest that this compound may have clinical use in humans, we were interested to know what effects NT69L had in primates. NT69L caused a potent antinociceptive effect against capsaicin (0.1 mg)-induced allodynia in 46 degrees C water in rhesus monkeys, inducing 40% of the maximal possible effect at an intravenous dosage of 0.03 mg/kg; its hypotensive effects precluded evaluation of higher dosages. Core temperature measured by rectal probe was modestly reduced at 0.01 and 0.03 mg/kg. In an intravenous self-administration procedure, NT69L was without reinforcing effects at any dose, including those that caused other pharmacological effects, and did not alter cocaine-maintained behavior when administered as a pretreatment.

Analgesics↗
PubMed2004

Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys.

Relatively few studies have assessed the reinforcing effects of hallucinogenic compounds, and no such studies have attempted to engender contingent responding for these compounds in animals with behavioral histories that include experience with serotonergically mediated reinforcing effects. The objectives of the present study were to investigate the capacity of several hallucinogenic compounds to maintain self-administration behavior in rhesus monkeys with a previous history of 3,4-methylenedioxymethamphetamine (MDMA) self-administration, and to compare these effects across a range of doses of drugs from two structural classes (indolealkylamines and phenylisopropylamines). The results indicate that no compound generated reliable responding and that no subject ever self-administered 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI) at rates above those engendered by contingent saline. However, 3 out of 4 subjects did respond at rates between 0.75 and 3.0 responses/s in one or more sessions where N,N-dimethyltryptamine (DMT), mescaline or psilocybin were available. During some of these sessions in which self-administration was maintained, animals earned a majority of all available infusions and appeared intoxicated by the end of the session. This pattern of transient self-administration may indicate that these compounds have weak reinforcing effects, or mixed reinforcing and aversive effects.

Amines↗
PubMed1998

Cocaine and alcohol synergism in taste aversion learning.

Female Long-Evans rats were given 20-min access to saccharin followed by injections of alcohol and cocaine, alone and in combination. Although there was no significant interaction between alcohol and cocaine when cocaine was given intraperitoneally (IP), aversions induced by the drug combination when cocaine was administered subcutaneously (SC) were significantly greater than those induced by either drug alone. Further, the aversions induced by the combination were significantly greater than the summed effects of the individual drugs administered alone, indicating a synergistic interaction between cocaine and alcohol. It was suggested that this synergism might result from a summation of the effects of alcohol, cocaine, and cocaethylene, a unique and toxic metabolite of cocaine produced when alcohol is coadministered. To assess the role of cocaethylene in the present design, additional taste aversion assessments were performed in which saccharin was paired with either IP or SC injections of cocaethylene. Although cocaethylene was found to induce aversions, the summed changes in consumption from baseline produced by cocaine, alcohol, and cocaethylene were significantly less than the changes produced by cocaine and alcohol in combination. These results indicate that the synergistic interaction between cocaine and alcohol in the present design cannot be attributed solely to summation of the effects of the individual drugs and the metabolite cocaethylene. Additional mechanisms by which cocaethylene might contribute to the synergistic interaction between cocaine and alcohol, as well as the role pharmacokinetic interactions between cocaine and alcohol might have in the interaction, were discussed.

Animals↗
PubMed1997

Effects of dopaminergic drugs on food- and cocaine-maintained responding. IV: Continuous cocaine infusions.

The effects of cocaine (continuously infused during the session with and without a are-loading dose) on responding maintained under multiple fixed-ratio 30 schedules of limited access to food and cocaine delivery (10 or 56 micrograms/kg per injection) were studied in nine rhesus monkeys. When responding was maintained by 10 micrograms/kg per injection, cocaine decreased rates of cocaine-maintained responding in a dose-related manner while having no effect on food-maintained responding. When responding was maintained by 56 micrograms/kg per injection, cocaine decreased both cocaine- and food-maintained responding. These results show that the effects of continuous infusions of cocaine depend upon both the unit dose of cocaine and the event that maintains responding. As such, the effects of continuous infusions of cocaine are similar to those of other, longer-acting dopamine agonists. Such results support the development of long-acting agonist approaches to the pharmacotherapeutic treatment of cocaine abuse.

Animals↗