Acute toxicity and gross behavioral effects of amphetamine, four methoxyamphetamines, and mescaline in rodents, dogs, and monkeys

Davis, William S.; Bedford, John A.; Buelke, Judith L.; Guinn, Meredith M.; Hatoum, Hind T.; Waters, I. W.; Wilson, Marvin C.; Braude, Monique C.

doi:10.1016/0041-008x(78)90027-3

Cited by 30 publications

(7 citation statements)

References 12 publications

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“…This is in accordance with Hardman et al (1973) who described LD50 in Sprague-Dawley rats to be 132 mg/kg after i.p injection, but in contrast with the findings of Speck (1957) who described in male albino rat the LD50 to be 370 mg/kg after i.p. administration and with Davis et al (1978) who described LD50 in male Sprague-Dawley rats to be 270 mg/kg i.p.. Speck (1957), in his study, described that flexor convulsions and respiratory arrest were the terminal events of animals; Davis et al (1978) described that rats were very inactive, hypoactive, they showed repetitive swimming-like movements, and that they had muscular weakness and ataxia. In our setting, we observed that animals elicited a flat body posture along with hyperlocomotion and almost no rearing.…”

Section: Discussionmentioning

confidence: 97%

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

Páleníček¹,

Balı́ková

Bubeníková-Valešová³

et al. 2007

Psychopharmacology

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Section: Discussionmentioning

confidence: 97%

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

Páleníček¹,

Balı́ková

Bubeníková-Valešová³

et al. 2007

Psychopharmacology

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“…As amphetamine and many other hallucinogens provoke abnormal locomotion in laboratory animals it has been suggested that this is a response to hallucination (Davis, Bedford, Buelke, Guinn, Hatoum, Waters, Wilson & Braude, 1978). This raises the possibility that not only catecholamine neurones but also 5-HT neurones are involved in the development of amphetamine psychosis and that backward walking in particular may be worth investigation as a potential animal model for human amphetamine psychosis, and therefore for paranoid schizophrenia which it closely resembles (Snyder, 1973;Woodrow et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

Backward Walking and Circling: Behavioural Responses Induced by Drug Treatments Which Cause Simultaneous Release of Catecholamines and 5‐hydroxytryptamine

Curzon¹,

Fernando²,

Lees³

1979

British J Pharmacology

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The roles of catecholamine and 5-hydroxytryptamine (5-HT) release in mediating backward walking and circling were studied in rats. 2 These behaviours occurred in animals given 15 mg/kg intraperitoneally of (+)-amphetamine (which predominantly releases catecholamines) or either p-chloroamphetamine or fenfluramine (which predominantly release 5-HT). They also occurred when smaller doses of (+ )-amphetamine (5 mg/kg) and either p-chloroamphetamine (2-5 mg/kg) or fenfluramine (5 mg/kg) were given together. 3 Characteristic dopamine-dependent behaviours (rearing, licking, gnawing) resulting from (+)-amphetamine injection were greatly reduced by p-chloroamphetamine or fenfluramine. 4 Characteristic 5-HT-dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p-chloroamphetamine or fenfluramine were unaffected by (+)-amphetamine. 5 Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)-amphetamine at low dosage. 6 Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5-HT release. 7 The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to L-DOPA treatment is discussed.

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“…Species variations in [DA] o and V max have important consequences for extrapolation of sensitivity to therapeutic, abused, and toxic drugs that require access to the DAT. Higher doses of the psychostimulants cocaine and D-amphetamine/methamphetamine are routinely required in rodents than in primates for experimental and neurotoxic actions (Davis et al, 1978;Melega et al, 1998); although they are caused in part by differing drug metabolism (Melega et al, 1998), dose differences may also result from underlying variation in DAT [or DAT/VMAT (Miller et al, 1999)] activity.…”

Section: Characteristics and Regional Heterogeneity In Single Pulse-ementioning

confidence: 99%

Dopamine Release and Uptake Dynamics within Nonhuman Primate StriatumIn Vitro

2000

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The putamen of the human striatum is a heterogeneous nucleus that contains the primary site of loss of dopamine (DA) in Parkinson's disease (PD). Furthermore, different functional domains of the putamen are heterogeneously susceptible to DA loss, and yet the dynamic regulation of extracellular DA concentration ([DA] o ) and comparison between domains has not been explored in the primate brain. In these studies, DA was measured in real time using fast-scan cyclic voltammetry at a carbon-fiber microelectrode in vitro in striatal sections from the common marmoset (Callithrix jacchus).[DA] o released by a single stimulus pulse varied threefold along a ventromedial-dorsolateral axis. DA uptake was via the DA transporter (GBR12909 sensitive, desipramine insensitive). On the basis of data modeling with simulations of Michaelis-Menten kinetics, rate maximum, V max , varied with region: both [DA] o and V max were greatest in regions most vulnerable in PD. These differences were reflected in part by regional variation in DA content. [DA] o , V max , and regional variation were two-to threefold greater than in rodent caudatoputamen.In addition, steady-state [DA] o at physiological firing rates in primate striatum was controlled by depolarization frequency, uptake, and presynaptic autoreceptors. Furthermore, regulation of [DA] o by these mechanisms differed significantly between limbic-and motor-associated domains.These data indicate interspecies heterogeneity in striatal DA dynamics that must be considered when extrapolating behavioral and drug responses from rodent to the primate brain. Moreover, the heterogeneity demonstrated within the primate putamen in the availability and dynamic regulation of DA may be central to understanding DA function in health, cocaine abuse, and disease.Key words: Parkinson's disease; basal ganglia; DA transporter; DA uptake; autoreceptor; cocaine The putamen of the primate striatum performs major sensorimotor, cognitive, and emotive functions. A central component of the basal ganglia, the putamen receives the main corticostriatal inputs from the motor, premotor, supplementary motor, and sensorimotor cortices (Kunzle, 1975(Kunzle, , 1977(Kunzle, , 1978Jones et al., 1977;Selemon and Goldman-Rakic, 1985). In turn, loss of dopaminergic innervation underlies the motor dysfunctions of Parkinson's disease (PD) (Hornykiewicz, 1966;Kish et al., 1988). Furthermore, studies using [18 F]-dopa positron emission tomography imaging, HPLC, and [ 3 H]-mazindol binding in PD and in intermediate primate 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP)-parkinsonism indicate that dopamine (DA) deinnervation follows a regionspecific pattern of vulnerability, beginning in dorsolateral putamen (Elsworth et al., 1987;Kish et al., 1988;Moratella et al., 1992;Antonini et al., 1995). The functions of the intact putamen are topographically compartmentalized along a dorsolateral-ventromedial axis (Haber and McFarland, 1999) with respect to corticostriatal (Kunzle, 1975(Kunzle, , 1977Selemon and Goldman-Rakic, 1985...

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Acute toxicity and gross behavioral effects of amphetamine, four methoxyamphetamines, and mescaline in rodents, dogs, and monkeys

Cited by 30 publications

References 12 publications

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

Mescaline effects on rat behavior and its time profile in serum and brain tissue after a single subcutaneous dose

Backward Walking and Circling: Behavioural Responses Induced by Drug Treatments Which Cause Simultaneous Release of Catecholamines and 5‐hydroxytryptamine

Dopamine Release and Uptake Dynamics within Nonhuman Primate StriatumIn Vitro

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