Direct self-administration

Self-administration studies can be initiated in one of two ways direct self-administration or substitution. In the direct self-administration procedure, inexperienced subjects are given access to a test drug, and the extent to which self-administration is initiated and maintained is measured and can be compared to the rate of behavior observed when placebo and/or other drugs are available. In the more commonly used substitution procedure, self-administration of a standard or prototypic abused drug is established first the test drug is then substituted for the standard drug, and changes in self-administration behavior are measured. 

Thiele TE, Marsh DJ, Ste Marie L, Bernstein IL, Palmiter RD (1998) Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 396 366-369 Thiele TE, Koh MT, Pedrazzini T (2002) Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor. J Neurosci 22 RC208 Thorsell A, Rimondini R, Heilig M (2002) Blockade of central neuropeptide Y (NPY) Y2 receptors reduces ethanol self-administration in rats. Neurosci Lett 332 1-4 Timmusk T, Palm K, Metsis M (1993) Multiple promoter direct tissue-specific expression of rat BDNF gene. Neuron 10 475-489... 

Stress and anxiety affect nicotine tolerance and dependence. The stress hormone corticosteroid reduces the effects of nicotine therefore, more nicotine is required to achieve the same effect. This increases tolerance to nicotine and leads to increased dependence. Animal studies have shown that stress can directly cause relapse of nicotine self-administration after a period of abstinence. Withdrawal symptoms of nicotine include irritability, impatience, hostility, anxiety, depressed mood, restlessness, increased appetite, and weight gain.2-4... 

The study of the role of DA in ethanol self-administration is affected by problems not dissimilar from those encountered with other drugs of abuse except that, in contrast to the fair consistency in one direction or in the other among studies on psychostimulants and opiates, much disagreement is registered in the case of ethanol. 

A criticism that can be raised towards the applicability of the above observations to the case of active drug self-administration is the fact that drug administration was passive i.e. noncontingent upon a response (Dworkin et al., 1992). The most direct way to address this issue is obviously that of monitoring changes in extracellular DA in animals actively... 

Where noncompliance, whether intentional or unintentional, is medically serious it becomes necessary to bypass self-administration (unsupervised) and to resort to directly observed (i.e. supervised) oral administration or to injection (e.g. in schizophrenia). 

Pressurized inhalation products have also been very successfully employed in the pediatric population to provide a drug directly to the desired site of action, the lung. These products are designed to deliver a unit dose at high velocity with small particle size, the ideal conditions for drug delivery to distal airways (92). Self-administration is difficult for younger patients without coordination. 

Some behavioural responses induced by nicotine were modified in mice lacking CBi cannabinoid receptors. Thus, whereas the severity of nicotine withdrawal syndrome was not affected in CBj knockout mice, the rewarding properties of nicotine, evaluated in the conditioned place preference assay, was abolished in these animals (Castane et al. 2003). In contrast, the absence of CBi cannabinoid receptors did not modify acute self-administration induced by nicotine (Cossu et al. 2001). The effective doses in these two behavioural models (acute intravenous self-administration and conditioned place preference) are different, which makes it difficult to directly compare the results of these studies. However, the interaction between THC and nicotine previously reported by using pharmacological and bio-... 

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