There's some studies that suggest microdosing amphetamine can increase dopamine receptor sensitivity, permanently. Though, this was done in rats so it may or may not translate to humans but it sounds promising nonetheless.
It seems even a single low dose of amphetamine is enough to produce long-lasting enhancements in dopaminergic activity. This can result in long-lasting benefits like:
Increased motivation
Improved focus
Increased energy
Improved mood
Decreased anhedonia
Improved learning
But it can also cause long-lasting adverse effects like
Motor tics
Impaired sleep quality
Anxiety
Restlessness
I tried taking 1.25 mg of Dexedrine (Dextroamphetamine) today and it's been about 3 hours since I took it and I'm feeling a little bit stimulated, but nothing big. According to one of the studies, dopamine increases after 3 days in the nucleus accumbens and continues increasing until week 3. I'll try to update this thread regularly.
Here are the studies:
[font=arial, helvetica, clean, sans-serif]A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats.[/font]
[font=arial, helvetica, clean, sans-serif]A single exposure to amphetamine (5 mg/kg, i.p.) caused context-independent sensitization of the locomotor effects of amphetamine, which intensified over time. Thus, sensitization to amphetamine was marginal at 3 d after treatment and more evident after 1 week, whereas 3 weeks after treatment, profound sensitization, as well as cross-sensitization, to cocaine was observed. Amphetamine pretreatment caused an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens, caudate putamen, and medial prefrontal cortex slices and of [(14)C]acetylcholine from accumbens and caudate slices. The hyperreactivity of dopaminergic nerve terminals appeared to parallel the development of locomotor sensitization, i.e., whereas hyperreactivity of accumbens dopaminergic terminals increased between 3 d and 3 weeks after treatment, the hyperreactivity of medial prefrontal dopaminergic terminals decreased.
http://www.ncbi.nlm.nih.gov/pubmed/10531460[/font]
[font=Verdana, arial, Helvetica, sans-serif]Long-Lasting Psychotomimetic Consequences of Repeated Low-Dose Amphetamine Exposure in Rhesus Monkeys[/font]
[font=Verdana, arial, Helvetica, sans-serif]The dopamine hypothesis of schizophrenia posits that dopamine dysregulation plays a key role in the etiology of schizophrenia. In line with this hypothesis, repeated amphetamine (AMPH) exposure has been shown to alter dopamine systems and induce behaviors reminiscent of positive-like and negative-like symptoms in both human and nonhuman primates. The mechanisms by which AMPH produces disturbances in brain function and behavior are not fully understood. The present study has employed a novel AMPH regimen, 12 weeks of intermittent escalating low doses of AMPH, to produce a nonhuman primate model for the purpose of elucidating the behavioral and neural consequences of excessive dopamine exposure. Behavioral responses to acute AMPH challenge (0.4–0.46 mg/kg) were assessed prior to and following the chronic 12-week treatment regimen, and, at present monkeys have been followed out to 28 months post-treatment. After chronic treatment, enhanced behavioral responses to AMPH challenge were readily apparent at 5 days postwithdrawal, and, were still present at 28 months postwithdrawal. The enhanced behavioral responses to low-dose AMPH challenge that were observed in the present study resemble closely the behavioral profile that has been described for chronic high-dose AMPH treatment in monkeys; i.e., hallucinatory-like behaviors, static posturing, and fine-motor stereotypies were all exacerbated in response to AMPH injection. In some animals, acute challenges after chronic AMPH evoked aberrant behavioral responses that lasted for 4 days. AMPH-treated monkeys also exhibited a significant decrease in the incidence of motor stereotypies in the off-drug periods between challenges. The present results are the first to document persistent long-term behavioral effects of intermittent exposure to repeated low-dose AMPH treatment in nonhuman primates. These findings may lay the groundwork for the development of a primate mode of psychosis with possible positive-like and negative-like symptoms.[/font]
http://www.nature.com/npp/journal/v20/n1/abs/1395233a.html
[font=arial, helvetica, clean, sans-serif]Long-lasting effects of escalating doses of d-amphetamine on brain monoamines, amphetamine-induced stereotyped behavior and spontaneous nocturnal locomotion.[/font]
[font=arial, helvetica, clean, sans-serif]The repeated intermittent administration of relatively low doses of amphetamine (AMPH) produces an enduring hypersensitivity to the motor stimulant effects of AMPH (behavioral sensitization), and this is accompanied by enhanced mesotelencephalic dopamine (DA) utilization/release. In contrast, chronic treatment with very high doses of AMPH does not produce sensitization, but is neurotoxic, resulting in the depletion of brain DA (and often other monoamines). However, gradually escalating doses of AMPH provide protection against the neurotoxic effects of higher doses given later. Therefore, the purpose of the present experiment was to determine if a regimen of gradually escalating doses of AMPH, culminating in much higher doses than usually used to study sensitization, would produce neural and behavioral changes associated with AMPH neurotoxicity (DA depletion) or behavioral sensitization (increased DA utilization). Female rats were given 60 injections (2/day) of increasing (1 to 10 mg/kg) doses of d-AMPH, culminating in rats receiving 20 mg/kg/day for four consecutive days. This treatment did not deplete brain DA or serotonin, but did produce a long-lasting enhancement (at least 12 days) in striatal and nucleus accumbens DOPAC concentrations, and DOPAC/DA ratios. These neurochemical changes were accompanied by an enduring hypersensitivity to the stereotypy-producing effects of a subsequent AMPH 'challenge.' In contrast to this enhanced response to a challenge, AMPH-pretreated rats showed a marked reduction in spontaneous nocturnal motor activity. It is concluded that rats can be given escalating doses of AMPH, which mimic to some extent the AMPH 'runs' common in addicts and that this produces neural and behavioral changes consistent with the development of sensitization; not neurotoxicity.[/font]
http://www.ncbi.nlm.nih.gov/pubmed/2440058
