Addiction discussed

Attention has been focused on dopamine because of its relationship to neurological diseases and to addiction (discussed in Section 10). Dopamine receptors constitute a large family, which are classified into two main subfamilies. The D, subfamily consists of D1a and D1B (D5) receptors and the D2 subfamily of D2, D3, and D4 receptors.763 764 The D, receptors, which are prominent in the prefrontal cortex and also in the striatum, are more abundant than the D2 receptors, which are also present in the striatum and the pituitary and are targets for antipsychotic drugs such as haloperidol (Fig. 30-33).765 The recently discovered and less numerous D3 receptors are present in only a few regions of the brain. However, a deficiency of D3 receptors may also be involved in addiction, schizophrenia, and Parkinson disease.766 767... 

More radical dissection of the morphine molecule was in progress concurrently with the work above. The chemistry of the series of analgesics that rely on an acyclic skeleton, the compounds related to methadone, is discussed earlier. Suffice it to say that this series of agents, with the possible exception of propoxyphene, seem to share abuse and addiction potential with their polycyclic counterparts. 

In the vertebrate CNS monoamines have been associated with a number of physiological functions (reviewed in Kandel et al., 1991). Serotonin has functions associated with mood, pain, sleep, learning, and memory. Dopamine has functions associated with schizophrenia, Parkinson s disease, and cocaine addiction. In vertebrates, dopamine is further metabolized into two additional neurotransmitters, norepinephrine and epinephrine. Norepinephrine increases the excitability of cells in response to sudden sensory input such as fear. Epinephrine has been identified in specific neurons of the brain, but the function of these cells is unknown. In addition, AADC has also been found in a class of neurons that do not have any of the four neurotransmitters discussed above (Jaeger et al., 1983). These neurons may use one of the trace amines, tyramine, tryptamine, or phenylethylamine, as a neurotransmitter. 

Addiction may result from inappropriate neuronal plasticity. As discussed in earlier sections of this chapter, drugs of abuse activate the same neuronal pathways as natural reinforcers. However, they do so in a strong and unregulated manner that is hypothesized to lead to abnormal engagement of learning and memory mechanisms, ultimately producing abnormal plasticity in neuronal circuits involved in motivation and decision-making. As a result, the addict becomes narrowly focused on compulsive, habitual behaviors associated with the addictive... 

TDM has improved the performance of anticancer, antidementia, antidepressant, antiepileptic, anticonvulsant, antifungal, antimicrobial, antipsychotic, antiretroviral, anxiolytic, hypnotic, cardiac, addiction treatment, immunosuppressant, and mood stabilizer drags for more than 30 years.2-9 Many analytical procedures evolved as analytical techniques and instrumentation have advanced. This chapter briefly reviews the different types of analytical methods the applications of high-throughput techniques in TDM are discussed in detail. 

The methods discussed above have been widely used to assess the effect of either continuous or intermittent nicotine on nAChR functions and brain biochemistry (Matta et al. 2007). For models of nicotine withdrawal, see the chapter by Malin in this volume. Given the intrinsic advantages and limitations of each approach, the non-contingent nature of most administration regimes and the absence of associated cues, it is important that these paradigms are not assumed to model tobacco addiction per se. Sometimes, the experiments are conducted in concert with behavioural measures (e.g. precipitation of withdrawal with somatic signs), which give more credibility to the assertion that a state of nicotine dependence has been achieved (Kenny and Markou 2005). 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

Within this Held, most of the research and results have been focused on the effects of drug therapy on the disorders induced by alcohol, and by the abuse of opiates. For a broader discussion of substance abuse see Chapter 18. In all instances of alcohol or drug abuse the first objective is to wean the patients from the addictive substance, treating or preventing the effects of withdrawal for those substances which cause physical dependence (alcohol, nicotine, opiates, caffeine, certain psychotropic agents such as benzodiazepines, possibly antidepressants). The second phase is the prevention of recurrence or relapse, which relies on a combination of social support, psychotherapy, and pharmacotherapy where available. In this respect, alcoholism is exemplary. 

Methadone (Dolophine) has an analgesic profile and potency similar to that of morphine but a longer duration of action and better oral bioavaUabUity. The kinetic properties of methadone and its derivative, LAAM, have been shown to be useful in the treatment of opioid addiction, as discussed in Chapter 35. 

I think most of the time this would be discussed either with a colleague in the addiction staff and it would be left to see what was the outcome of the next week is going to be or, if it was important they would get in... 

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