Chronic administration

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Dependence is a somatic state which develops after chronic administration of certain dtugs. This condition is characterized by the necessity to continue administration of the drug to avoid the appearance of withdrawal symptoms. Withdrawal symptoms are relieved by the administration of the drug upon which the body was dependent . Psychological dependence is due to (e.g., social) reinforcement processes in the maintenance of drug-seeking behavior. 

Chronic administration of opiates and alcohol leads to physical dependence a phenomenon, which is only weakly expressed following chronic administration of psychostimulants or other drugs of abuse. Physical dependence results from neuroadaptive intracellular changes to an altered pharmacological state. Abstinence from chronic opiate or alcohol use leads to a variety of physiological and psychological withdrawal symptoms based on these adaptations of the neuronal system. 

Chronic administration of ethanol may up-regulate L-type and N-type VGCCs—an effect that may contribute to ethanol withdrawal symptoms (Kahkonen and Bondarenko 2004 McMahon et al. 2000), probably through involvement of NMDA receptors and other neural circuitry (Calton et al. 1999). 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

Diagnostic criteria for inhalant use disorders in DSM-IV-TR are similar to those in the International Classification of Diseases, Tenth Revision (ICD-10) (World Health Organization 1992). These criteria include biological, cognitive, and behavioral dimensions. The DSM-IV-TR diagnosis of inhalant dependence is given when three or more of the seven criteria are present (see Table 8-2). The first criteria to be considered here are tolerance and withdrawal. These phenomena are considered to be forms of adaptation to chronic administration of these compounds and were discussed extensively earlier in this chapter. 

Weereratne, E. A. H., Gregoriadis, G., and Crow, J. (1983). Toxicity of sphingomyelin-containing liposomes after chronic administration in mice, Br. J. Exp. Pathol.. 64, 670-676. 

Chiodi, LA and Bunney, BS (1983) Typical and at q)ical neuroleptics differential effects of chronic administration on the activity of A9 and AlO midbrain dopamine neurones. J. Neurosci. 3 1607-1619. 

Figure 19.1 The elevated plus-maze. (Top) The apparatus is arranged with two open arms, two closed arms and a central zone, raised above the ground. Animals are placed in the central zone (usually facing an open arm) and their movements scored for number of entries to the open and closed arms and the percentage time spent in the open arms. (Bottom) Chronic administration (5 days) of the anti-anxiety drug, chlordiazepoxide, increases the percentage time spent on the open arms to approximately 50% of the total. (Figure kindly provided by S. E. File)...

These observations question the role of noradrenaline as an initiator of anxiety as does the finding that the anti-anxiety drug, buspirone (see Chapter 9), increases the concentration of noradrenaline in the extracellular fluid in the frontal cortex of freely-moving rats (Done and Sharp 1994). Whether this is because buspirone is metabolised to l-(2-pyrimidinyl)-piperazine (1-PP), which is an a2-adrenoceptor antagonist, is uncertain. Unfortunately, no studies have investigated the effects of chronic administration of this drug on noradrenergic transmission this could be important because, unlike benzodiazepines, buspirone is effective therapeutically only after several weeks of treatment. 

Margules, DL and Stein, L (1968) Increase of antianxiety activity and tolerance of behavioural depression during chronic administration of oxazepam. Psychopharmacologia 13 74—80. 

NEUROBIOLOGICAL CHANGES INDUCED BY CHRONIC ADMINISTRATION OE ANTIDEPRESSANTS... 

More importantly for this discussion is the finding that chronic administration of an antidepressant produces a similar increase in the concentration of extracellular 5-HT in the terminal field together with recovery of neuronal firing. Presumably this is because the prolonged elevation of extracellular 5-HT around the neurons in the Raphe causes progressive desensitisation of the somatodendritic 5-HTia receptors. At this point, inhibition of their firing does not occur and so more 5-HT is released in the cortex (see Hervas et al. 1999). 

Table 20.7 Neurochemical changes generally found after chronic administration of antidepressant drugs or repeated electroconvulsive shock...

Carney, J.M., Starke-Reed, P.E., Oliver, C.N., Landrum, R.W., Cheng, M.S. and Wu, J.F. (1991). Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-cr-phenylnitrone. Proc. Natl Acad. Sci. USA 88, 3633-3636. 

Somatosensory cortical, pyramidal cells die at a very high rate with chronic administration. It seems to me that the involvement of dopamine in that is... 

The reasons for the deerease in DA uptake sites are not clear at present. Preliminary immunoeytoehemieal data indieate that there are no changes in the density or morphology of eatecholamine axons after chronic administration of MDMA or MDA (O Heam et al. 1988). 

Flint, B.A. and Ho, I.K. Tolerance development to phencyclidine by chronic administration. Prog Neuropsvchopharmacol 4 233-239,... 

Goodwin, P.J. Perez, V.J. Eatwell, J.C. Palet, J.L. and Jaworski, M.T. Phencyclidine Effects of chronic administration in the female mouse on gestation, maternal behavior, and the neonate. Psvchopharmacoloav (Berlin) 69 63-67, 1980. 

Slow-transit constipation can be treated with chronic administration of osmotic laxatives. Tegaserod maleate 6 mg orally twice daily is an acceptable treatment. Senna, bisacodyl, and other stimulants should be used only when the others fail to deliver the desired effect. 

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