Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses.

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

Understanding the relationship between the molecular mechanisms underlying neurotoxicity of high-dose methamphetamine (METH) and related clinical manifestations is imperative for providing more effective treatments for human METH users. This article provides an overview of clinical manifestations of METH neurotoxicity to the central nervous system and neurobiology underlying the consequences of administration of neurotoxic METH doses, and discusses implications of METH neurotoxicity for treatment of human abusers of the drug.

https://jpet.aspetjournals.org/content/jpet/362/3/474.full.pdf

Molecular, Behavioral, and Physiological Consequences of Methamphetamine Neurotoxicity: Implications for Treatment.

http://www1.ci.uc.pt/pessoal/anabrett/pdfs/PDF-2010/141-Ecstasy-Bioelectrochemistry.pdf

Electrochemical oxidation of amphetamine-like drugs and application to electroanalysis of ecstasy in human serum.

Aims There are no studies directly comparing self-administration of methamphetamine and d-amphetamine by humans. This study compared intranasal methamphetamine- and d-amphetamine self-administration and characterized the mood, performance and physiological effects produced by the drugs.



Design  A randomized, double-blind, placebo-controlled, cross-over study.



Setting  An out-patient research unit at the New York State Psychiatric Institute.



Participants  Male recreational methamphetamine users (n = 13).



Measurements  Five 2-day blocks of sessions were conducted. On the first day of each block, participants ‘sampled’ a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamine plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money).



Findings  There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines increased self-administration dose-dependently, with 41% drug choices overall. Under the $20 condition, only 17% drug options were selected. Both drugs increased cardiovascular activity and ‘positive’ mood, although methamphetamine produced more prominent effects on some measures (e.g. heart rate and ratings of ‘high’).



Conclusions  Methamphetamine and d-amphetamines appear to produce a similar dose-related profile of effects in humans, which supports their equivalence for abuse potential.

/pdf/comparison-of-intranasal-methamphetamine-and-d-amphetamine-1doyo7ltf2.pdf

Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans.

In this work, the ion transfer mechanism of the anticancer drug daunorubicin (DNR) at a liquid/liquid interface has been studied for the first time. This study was carried out using electrochemical techniques, namely cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The lipophilicity of DNR was investigated at the water/1,6-dichlorohexane (DCH) interface, and the results obtained were presented in the form of an ionic partition diagram. The partition coefficients of both neutral and ionic forms of the drug were determined. The analytical parameter for the detection of DNR was also investigated in this work. An electrochemical DNR sensor is proposed by means of simple ion transfer at the water/DCH interface, using DPV as the quantification technique. Experimental conditions for the analytical determination of DNR were established, and a detection limit of 0.80 μM was obtained.

Electrochemical Study of the Anticancer Drug Daunorubicin at a Water/Oil Interface: Drug Lipophilicity and Quantification

https://repositorio-aberto.up.pt/bitstream/10216/49750/2/60361.pdf

Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions.

Aluska Helguera Morales

Papers

Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions.