Behavioral effects

Stimulants induce both tolerance and sensitization to their behavioral effects. Tolerance develops to the anorectic and euphoric effects of stimulants (Schuster 1981) however, chronic intermittent use of low doses of stimulants delays the development of tolerance. With the doses commonly used in clinical practice, patients treated for narcolepsy or for depressive or apathetic states find that the stimulant properties usually persist without development of tolerance however, the persistence of antidepressant effects remains a matter of controversy. Sensitization has been linked to the development of amphetamine-induced psychosis (Yui et al. 1999). Sensitization to the induction of psychosis is suggested because psychosis is induced by progressively lower doses and shorter periods of consumption of amphetamine following repeated use over time (Sato 1986). Sensitization for amphetamine-induced psychosis may persist despite long periods of abstinence. 

The development of psychosis is the most striking clinical characteristic of high-dose stimulant abuse. The amphetamines, methylphenidate, and phen-metrazine all produce psychosis (Ellinwood et al. 1973 Harris and Batki 2000 Iversen et al. 1978 Lucas and Weiss 1971 McCormick and McNeil 1962). 

Dependence and withdrawal can occur with all of the stimulants. Cocaine is one of the most strongly reinforcing drugs in self-administration paradigms in animals and also has a psychological withdrawal syndrome. A typical pattern of withdrawal includes a ravenous appetite, exhaustion, and mental depression, which may last for several days after the drug is withdrawn. Because tolerance develops quickly, abusers may take large doses, compared with those used medically, for example, as anorexiants. 

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AHopregnanolone and similar A-ring-reduced pregnanes potentiate GABA effects at these receptors. These steroids mimic the effects of the benzodiazepines, changing chloride ion conductance and producing sedative and hypnotic behavioral effects (276,277). Neuroactive steroids can be therapeutically useful as anticonvulsants, anxiolytics, or anesthetics (qv) (see also Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

The mechanism of action of nootropic agents has been proposed to be their abiUty to faciUtate information acquisition, consoHdation, and retrieval (36). No one particular effect has been observed with any consistency for these agents, thus whereas a considerable amount of diverse preclinical pharmacological behavioral data has been generated using these compounds, the significance of these results in predicting clinical efficacy has not been established (43,44). Reviews on the biochemical and behavioral effects of nootropics are available (45—47). 

The vomeronasal organ (VNO), located in the nose, is a small chemical sensing stmcture associated with odors and behavioral effects. The vomeronasal system, which is made up of the VNO and a portion of the brain s limbic system, is stmcturaHy independent of the olfactory and nervous terminalis systems in the nose. It may, however, interact with these systems in a manner dependent on prior experience or learning, and therefore be direcdy related to the association of smells and experiences. This independent chemosensory system in the nose may prove to open doors to new learning associated with the sense of smell and human behavior. 

Psychostimulants are drugs that substantially influence cognitive and affective functioning and behaviors. Effects are increased motivational desire, agitation, heightened vigilance, euphoria, hyperactivity, and... 

The characteristic behavioral effects of acute and chronic psychomotor stimulant diugs are locomotor activation, stereotypy, and conditioned reward and stimulus-reward learning. The most important brain regions involved in these effects are summarized in Table 3. 

The assumptions behind this calculated example are a considerable oversimplification of the real migration behavior. Effects such as diffusion into the rock matrix, dilution with inflowing water, dispersion of the migration front, channeling of the host... 

Anton RF, Pettinati H, Zweben A, et al A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence. J Clin Psychopharmacol 24 421 28, 2004 Aragon CM, Stotland LM, Amit Z Studies on ethanol-brain catalase interaction evidence for central ethanol oxidation. Alcohol Clin Exp Res 15 165-169, 1991 Arizzi MN, Correa M, Betz AJ, et al Behavioral effects of intraventricular injections of low doses of ethanol, acetaldehyde, and acetate in rats studies with low and high rate operant schedules. Behav Brain Res 147 203—210, 2003 Azrin NH, Sisson RW, Meyers R, et al Alcoholism treatment by disulfiram and community reinforcement therapy. J Behav Ther Exp Psychiatry 13 105—112, 1982 Babor TF, Kranzler HR, Lauerman RL Social drinking as a health and psychosocial risk factor Anstie s limit revisited, in Recent Developments in Alcoholism, Vol 5. Edited by Galanter M. New York, Plenum, 1987, pp 373 02... 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Garrett BE, Griffiths RR The role of dopamine in the behavioral effects of caffeine in animals and humans. Pharmacol Biochem Behav 57 533—541, 1997... 

Martin WR, Sloan JW, Sapira JD, et al Physiologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phenmetrazine, and methylphenidate in man. Clin Pharmacol Ther 12 245-258, 1971 McCormick TC Jr, McNeil TW Acute psychosis and Ritalin abuse. Tex State J Med... 

Crowder LA, Lanzaro GC, Whitson RS. 1980. Behavioral effects of methyl parathion and toxaphene exposure in rats. J Environ Sci Health B15 365-378. 

Neurotoxic compounds can have behavioral effects in the field (see Chapters 5, 9, and 15), and these may reduce the breeding or feeding snccess of animals and their ability to avoid predation. A number of the examples that follow are of sub-lethal effects of pollutants. The occurrence of sublethal effects in natural populations is intimately connected with the question of persistence. Chemicals with long biological half-lives present a particular risk. The maintenance of substantial levels in individuals, and along food chains, over long periods of time maximizes the risk of sublethal effects. Risks are less with less persistent compounds, which are rapidly... 

From an ecotoxicological point of view, it has often been suspected that sublethal effects, such as those described here, can be more important than lethal ones. Both p,p -DDT and p,p -DDD are persistent neurotoxins, and may very well have caused behavioral effects in the field. This issue was not resolved when DDT was widely used, and remains a matter for speculation. More is known, however, about eggshell thinning caused by p,p -DDE and its effects upon reproduction, which will be discussed in Section 5.2.5.I. 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

CBs, like OPs, can cause a variety of sublethal neurotoxic and behavioral effects. In one study with goldfish Carrasius auratus), Bretaud et al. (2002) showed effects of carbofuran on behavioral end points after prolonged exposure to 5 pg/L of the insecticide. At higher levels of exposure (50 or 500 pg/L), biochemical effects were also recorded, including increases in the levels of norepinephrine and dopamine in the brain. The behavioral endpoints related to both swimming pattern and social interactions. Effects of CBs on the behavior of fish will be discussed further in Chapter 16, Section 16.6.1. 

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