Animal studies behavior

SPACEEIL has been used to study polymer dynamics caused by Brownian motion (60). In another computer animation study, a modified ORTREPII program was used to model normal molecular vibrations (70). An energy optimization technique was coupled with graphic molecular representations to produce animations demonstrating the behavior of a system as it approaches configurational equiHbrium (71). In a similar animation study, the dynamic behavior of nonadiabatic transitions in the lithium—hydrogen system was modeled (72). 

From the limited data on the kinetics and distribution of liposomes in man (Zonneveld and Crommelin, 1988) it can be concluded that the overall behavior of liposomes in man is similar to that observed in animals. Studies in cancer patients showed predominant lirer and spleen uptake of technetium-labeled liposomes (Richardson et al.,... 

Animal studies have shown that the periodic dosing regimen often leads to behavioral augmentation or sensitization in animals (Post 1981). 

The close resemblance between schizophrenia and PCP-induced psychosis suggests that the behavioral effects produced by PCP might be useful as a model of psychosis. On this basis, most animal studies have examined the ability of various agents to modify PCP-induced hyperactivity and stereotypy. While some studies suggest that neuroleptics such as haloperidol (Castellani and Adams 1981 Garey et al. 1980), chlorpromazine, or clozapine (Freed et al. 

Based on the data from animal studies, diisopropyl methylphosphonate is principally excreted in the urine as the metabolite IMPA (Hart 1976 Ivie 1980). Chromatographic behavior of urinary metabolites does not change after the urine is treated with glucuronidase and sulfatase, so there is no conjugation of diisopropyl methylphosphonate or IMPA by microsomal enzymes (Hart 1976). There was minimal excretion of diisopropyl methylphosphonate metabolites in bile (Hart 1976) or in the milk of a lactating cow (<1%) (Palmer et al. 1979). 

The overall evidence from studies in animals supports the observations of lead neurobehavioral effects in humans. As pointed out by Cory-Slechta (1995), studies in animals have provided a direct measurement of the behavioral process per se, and have done so in the absence of the covariates (e.g., socioeconomic status, parental IQ) known to affect IQ scores in human studies. It is also worth noting that animal studies, in which the experimental design is carefully controlled, have shown that the timing of exposure is crucial, that different neurobehavioral outcomes are affected differently (different thresholds), and that some behavioral alterations last longer than others. 

Animal studies support he human evidence of neurobehavioral toxicity from prenatal exposure to low levels of lead. In an extensive review of the literature, Davis et al. (1990) discussed similarities between human effects and those in animals. The authors concluded that qualitatively "... the greatest similarities between human and animal effects involve cognitive and relatively complex behavioral processes such as learning." They further reported that quantitative relationships for PbB levels across species that cause developmental neurobehavioral effects are 10-15 pg/dL in children, <15 pg/dL in primates, and <20 pg/dL in rodents. 

Bomschein RL, Pearson D, Reiter L. 1980. Behavioral effects of moderate lead exposure in children and animal models Part 1. Clinical studies Part 2. Animal studies. CRC Crit Rev Toxicol 43-152. 

Animal studies indicate that nutritional deficiencies in a number of essential elements (e.g., calcium, iron, zinc, copper, phosphorus) may impact the toxicokinetic and toxicological behavior of lead (ATSDR 1993 Chaney et al. 1989). In infants and children, lead retention has been shown to be inversely correlated with calcium intake (Johnson and Tenuta 1979 Sorrell et al. 1977 Ziegler et al. 1978). Zinc has been shown to have a protective effect against lead toxicity in a number of animal species (Goyer 1986 Haeger-Aronsen et al. 1976 Brewer et al. 1985 Cerklewski and Forbes 1976). 

N,N-Dialkyltryptamines bearing an alkyl substituent on the aromatic nucleus have not been evaluated in man, and only data from animal studies are available. Taborsky et al. (228) found 1-methylation to have variable effects on behavioral activity. This might reflect blood-brain barrier permeability. Methylation at the N1 position of DMT (37), to give 1, N,N-trimethyltryptamine (1-TMT), had... 

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

There are only two reports of the human evaluation of a 6-hydroxylated N,N-dialkyltryptamine. Szara and Hearst (223) studied the effects of 6-hydroxy-N,N-diethyltryptamine (6-OH-DET 56) in a single subject. Doses of 1 and 2 mg were inactive a 5-mg dose produced a short-lasting perceptual disturbance and a 10-mg dose, after 1 hr, produced some psychotomimetic disturbances. Rosenberg et al. (182) compared the activity of DMT with that of 6-OH-DMT (55) in five human subjects. While DMT was active, the 6-hydroxy derivative was found to be inactive at intramuscular doses of approximately 50 to 75 mg. At a dose of 10 mg/kg, 6-OH-DMT (55) increased spontaneous activity in mice more so than a comparable dose of DMT 6-OH-DET (36) was essentially equiactive with DET in this respect (224). In most other animal studies, however, 6-hydroxylation of DMT has been observed to result in a decrease or complete loss of behavioral activity (228,236-238). The behavioral potency of 5-OMeDMT (59) was also reduced by 6-hydroxylation (226). 7-Hydroxy-N,N-dimethyltrypt-amine (7-OH-DMT 57) has not been evaluated in man. At an intraperitoneal dose of 33 jtM/kg, 7-OH-DMT displayed no behavioral effects in rats (228). The pharmacologic effects of all four hydroxylated derivatives of DMT, psilocin (49), bufotenine (53), 6-OH-DMT (55), and 7-OH-DMT (57) have been compared in studies by Taborsky et al. (228) and by Cerletti et al. (29). 

Based on the foregoing discussion, it is possible to formulate some structure-activity relationships with respect to the behavioral properties of various trypt-amine derivatives. It should be noted that these structure-activity relationships are derived from the results of both human and animal studies. 

Methoxy-N,N-dimethyltryptamine (O-methylbufotenine 59) is hallucinogenic in man at a parenteral dose of approximately 6 mg (204). Numerous animal studies have shown that 5-OMeDMT is behaviorally quite active (16,65-67,71,178,184). This compound also produced limb-flick behavior in cats (119) and the serotonin syndrome in rats (209). Glennon et al. (85) demonstrated that 5-OMeDMT serves as a discriminative stimulus in rats and have employed rats trained to discriminate 5-OMeDMT from saline to investigate the structure-activity relationships of various substituted N,N-dialkyltryptamine derivatives. The results of these studies have recently been reviewed (84). 

Practical and ethical issues have impeded the analysis of biochemical influences on human behavior, and at present questions are more common than answers. However, in conjunction with more readily controlled animal studies, patterns of relationships between hormones and behavior have begun to emerge. 

Because neuropeptides are active in very small amounts within the CNS they are more difficult to manipulate and study than steroid hormones. In addition, at present there is no simple method for administering neuropeptides within the CNS. (In animals, it is necessary to inject chemicals or their antagonists directly into the CNS, which is not feasible in humans.) Thus, most research on the behavioral effects of either oxytocin or vasopressin in humans is correlational, and subsequently difficult to interpret. However, animal studies also support the hypotheses described here (Carter, 1992 Uvnas-Moberg, 1996). 

Behavioral and emotional effects In animal studies, ginseng does not prolong pentobarbital-induced sleep, nor does it affect spontaneous locomotion (Mitra et al. 1996). It does potentiate amphetamine-induced locomotion, but it reduces the stereotypy and lethality caused by amphetamine. Ginseng has analgesic effects, which are discussed at greater length in chapter 8. Catalepsy induced by haloperidol is potentiated by ginseng, while the hyperthermic effect of 5-HTP is attenuated. No antiseizure effects have been observed. 

Cognitive effects Animal studies There is an extensive literature that deals with the effects of ginseng on memory, learning, and behavior (Gillis 1997 Wang et al. 1995). However, ginseng extract (G115) failed to show anxiolytic effects in an animal model (Petkov et al. 1987)... 

As with almost all lawn chemicals, the long-term human effects of exposure to 2,4-D remain entirely unclear. Laboratory animal studies have shown that the chemical can migrate into nerve tissues and accumulate in the brain, with resulting behavioral changes in test rats. Whether the chemical is a potential... 

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