Cocaine binding sites related to drug self-administration.
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Amphetamine↗
Biomedical subjects
J W Boja
Publications and source records attributed to J W Boja.
Lack of generalization of nisoxetine with amphetamine in the rat.
Rats were trained to discriminate between the stimulus properties of intraperitoneally administered d-amphetamine (0.8 mg/kg) and its vehicle in a two-lever, food-motivated operant task. Once trained, doses of the norepinephrine reuptake inhibiting agent nisoxetine, ranging from 10 to 20 mg/kg, were administered to investigate if the amphetamine-trained rats would generalize to this agent. This did not, however, occur. Thus, it would seem that noradrenergic mechanisms have a negligible role in the production of the amphetamine-induced discriminative stimulus cue in the rat. Previous evidence that indicated a noradrenergic mediation of amphetamine discrimination in the mouse contrasted with the present results in rats and this discrepancy should warrant caution in comparing results of discriminative studies in these two species.
Animals↗
CGS 10746B is able to attenuate the effects of amphetamine: further evidence for dopaminergic mediation.
Previous results indicate that agents which either decreases synthesis or block postsynaptic dopamine receptors will attenuate the discriminative stimulus produced by d-amphetamine. CGS 10746B has been reported to decrease dopamine release without changing its metabolism or occupying its receptors. In the present study, rats successfully trained to discriminate intraperitoneally administered (0.8 mg/kg) d-amphetamine in a two-lever, food-motivated operant task were observed to be unable to discriminate amphetamine when pretreated with 30 mg/kg CGS 10746B. This antagonism was shown to be dose-responsive and constitutes a third mechanism, i.e., dopamine release inhibition, that evidences the dopaminergic mediation of amphetamine in the discriminative paradigm. When both cathinone (0.8 mg/kg) and cocaine (10.0 mg/kg) were administered to the amphetamine-trained rats they each were recognized as amphetamine and are, thus, considered to generalize to the amphetamine discriminative stimulus. Coadministration of CGS 10746B and cathinone totally antagonized this generalization, whereas pretreatment with CGS 10746B prior to cocaine significantly reduced cocaine's effects. These results implicate dopamine mechanisms in the discriminative stimulus properties of the psychostimulants amphetamine, cathinone and cocaine.
Alkaloids↗
Norfenfluramine, the fenfluramine metabolite, provides stimulus control: evidence for serotonergic mediation.
Nine male rats were trained to discriminate 1.4 mg/kg norfenfluramine (NF) from its vehicle using a two-lever, food-motivated, operant discrimination task. Once trained, the rats showed a dose-dependent decrease in responding on the NF-correct lever following decreased doses of NF (ED50 = 0.71 mg/kg). Administration of 2.0 mg/kg fenfluramine (FEN) produced 100% responding on the NF-correct lever and decreasing doses of FEN, likewise, produced a dose-dependent decrease in responding on the NF-correct lever (ED50 = 1.30 mg/kg). Time-course data indicated that NF has a fast onset and a peak effect at 20-60 min after administration. Analysis of the time-course data provided a half-life of approximately 8 hr. In contrast, FEN did not show the rapid onset that was observed with NF. However, NF had a similar peak effect and half-life. These results indicate a pharmacological similarity between NF and FEN. However, the difference in onset of action suggests a possible difference between the parent drug and its metabolite. The serotonergic agonists mCPP, DOI, 5-MeODMT and LSD generalized to 1.4 mg/kg NF, whereas neither TFMPP nor 8-OHDPAT generalized to NF. The dopaminergic agonist AMPH also did not generalize to NF. The implications of these findings are discussed.
Animals↗
Behavioral suppression following 3,4-methylenenedioxymethamphetamine.
Rotation in rats was employed as an assay of the central dopaminergic activity of 3,4-methylenedioxymethamphetamine (MDMA). This agent was observed to possess predominantly amphetamine-like actions at low doses. However, at higher doses it also appears to stimulate the dopamine receptor directly. Following a third dose of MDMA, a significant decrease in rotation was evident to this drug and to amphetamine, suggesting a neurotoxic or long-term suppressive action of MDMA.
3,4-Methylenedioxyamphetamine↗
Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE").
Eight male rats were trained to discriminate 2.0 mg/kg N-ethyl-3,4-methylenedioxyamphetamine (MDE) from its vehicle using a two-lever, food-motivated operant discrimination task. Once trained, the rats showed a dose-dependent decrease in discriminative accuracy following administration of decreased doses of MDE (ED50 = 0.75 mg/kg). Administration of 1.5 mg/kg 3,4-methylenedioxymethamphetamine (MDMA), a recently restricted Schedule I drug, produced 100% MDE-appropriate responding in the MDE-trained rats and decreased discriminative performance was similarly observed following lower doses of MDMA (ED50 = 0.62 mg/kg). The difference in relative potencies of MDE and MDMA in rats is reminiscent of those seen in human abusers who report effective oral psychotomimetic doses. Time-course data indicated that MDE has a fast onset, 100% drug-correct responding 10 min post-injection, and a peak effect between 10-20 min with declining effect at 60-120 min post-administration. These findings along with those of others show a pharmacological similarity between MDE and MDMA. Implications as to the future scheduling of MDE are discussed.
3,4-Methylenedioxyamphetamine↗
A novel, adaptable and inexpensive computerized activity meter.
A number of activity meters ranging from fully manual to fully automated have been described. A computerized activity meter, used primarily as a rotational activity chamber, is described. This inexpensive system is built around a Commodore 64 computer interfaced through a circuit board to the meters. Each computer can run four chambers and, as a rotometer, can distinguish quarter and full turns in either direction. The system is easily adapted to record data from various behavioral chambers, including an open field with photocell beams.
Animals↗
Acute low-level formaldehyde behavioural and neurochemical toxicity in the rat.
The purpose of the present study was to determine the effects of low-level formaldehyde exposure upon behavior and neurochemistry in the male rat. Rats were exposed to either air or formaldehyde vapor (5, 10 or 20 parts per million) for 3 hours on 2 consecutive days during which behavioral observations were made. Following the second exposure session the rats were sacrificed and their brains analyzed for norepinephrine, dopamine, 5-hydroxytryptamine and their major metabolites. Formaldehyde exposure resulted in decreased motor activity and neurochemical changes in dopamine and 5-hydroxytryptamine neurons.
Animals↗
Brain reactive antibodies and the blood-brain barrier: observations in aging rodents and the effects of peripheral kainic acid.
This study was initiated to confirm the existence of brain-reactive autoantibodies and to determine if such antibodies have higher affinity for brain regions especially affected in Alzheimer's disease. Serum collected from 90, 300, and 600 day old mice was incubated against brain tissues from these same mice, followed by incubation with fluorescently tagged rabbit antimouse IgG. No antibodies were present in the youngest serum, but considerable antibodies were present at 300 and, especially, at 600 days. Such antibodies were present in the blood vessels, but not in the brains of older animals. These antibodies, applied exogenously, labeled cells equally in all three ages of brains including most cortical and many other neurons, indicating that they are not neurotransmitter specific. In a further study, kainic acid or saline was administered peripherally to 15-month old rats. Kainic acid damaged the blood brain barrier and allowed the CNS entry of brain-reactive antibodies, especially into the subregions of hippocampus most damaged in Alzheimer's.
Aging↗