Posted 22 March 2009 - 10:33 AM
pros: improved catecholaminergic neuron activity*
much more specific, can be timed to activity one wants to reinforce, as opposed to always-on effect of deprenyl
cons: no propargyl group like deprenyl to upregulate enzyme activity
short, reversable MAO inhibition doesn't give 24/7 protection against MAO-produced toxins
at least in stroke, also evidence in pre-adolescence. not a lot of money to give 'healthy' people amphetamine, at least in moderate dosages. i think most useful for time when trying to instigate behavioral changes.
Enhanced Neocortical Neural Sprouting, Synaptogenesis, and Behavioral Recovery With D-Amphetamine Therapy After Neocortical Infarction in Rats
R. Paul Stroemer, PhD; Thomas A. Kent, MD; Claire E. Hulsebosch, PhD
From the School of Biological Sciences, Division of Neuroscience, University of Manchester, Manchester, England (R.P.S.), and Departments of Neurology (T.A.K.) and Anatomy and Neurosciences and Marine Biomedical Institute (C.E.H.), University of Texas Medical Branch, Galveston.
Correspondence to Dr C.E. Hulsebosch, Department of Anatomy and Neurosciences, 301 University Blvd 1069, University of Texas Medical Branch, Galveston, TX 77555-1069. E-mail CEHulseb@utmb.edu
Background and Purpose—D-Amphetamine administration increases behavioral recovery after various cortical lesions including cortical ablations, contusions, and focal ischemia in animals and after stroke in humans. The purpose of the present study was to test the enhanced behavioral recovery and increased expression of proteins involved in neurite growth and synaptogenesis in D-amphetamine–treated rats compared with vehicle-treated controls after a focal neocortical infarct.
Methods—Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n=8 per time point per group) by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery in 2 groups of rats: D-amphetamine treated (2 mg/kg IP injections) and vehicle treated (saline IP injections). To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, growth-associated protein (GAP-43), a protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques, and both density and distribution of reaction product were measured. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function using the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies during the period of drug action and 24 hours later. A Morris water maze and other indices of behavioral assays were also measured similarly. Recovery times were 3, 7, 14, 30, and 60 days postoperatively.
Results—Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in density and distribution of immunoreaction product as determined by optical density measurements in the neocortex of the infarcted group treated with D-amphetamines compared with vehicle-treated infarcted controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction only at days 3, 7, and 14. By contrast, the synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions ipsilateral to the infarction as well as increased distribution in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated that improved recovery of forelimb placement on the side contralateral to the infarction was statistically significant in the D-amphetamine–treated group compared with the vehicle-treated group (P<0.025). Spatial memory, as measured with the Morris water maze, worsened in the vehicle-treated group compared with the D-amphetamine–treated group at 60 days (P<0.025).
Conclusions—These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex in a pattern that corresponds both spatially and temporally with behavioral recovery that is accelerated by D-amphetamine treatment. While the specific mechanisms responsible for D-amphetamine–promoted expression of proteins involved in neurite growth and synaptogenesis and of enhanced behavioral recovery are not known, it is suggested that protein upregulation occurs as a result of functional activation of pathways able to remodel in response to active behavioral performance.
also, this was interesting:
Noradrenaline provides long-term protection to dopaminergic neurons by reducing oxidative stress
Jean-Denis Troadec,* Marc Marien,† Frédéric Darios 1 , Andreas Hartmann,* Merle Ruberg,* Francis Colpaert† and Patrick P. Michel,*,†
*INSERM U289, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, Paris, France
†Centre de Recherche Pierre Fabre, Castres, France
Address correspondence and reprint requests to Patrick P. Michel, INSERM U289, Hôpital de la Salpêtrière, 47 boulevard de l'hôpital, 75013, Paris, France. E-mail: firstname.lastname@example.org
Copyright International Society for Neurochemistry
catechol • dopamine neurons • neuroprotection • noradrenaline • oxidative stress
To better understand the neurotrophic function of the neurotransmitter noradrenaline, we have developed a model of mesencephalic cultures in which we find low concentrations (0.3–10 µm) of noradrenaline to be remarkably effective in promoting long-term survival and function of dopaminergic neurons. This protective action reproduced the effect of caspase inhibition. It was atypical in that it occurred independently of adrenoceptor activation and was mimicked by some antioxidants, redox metal chelators and the hydroxyl radical detoxifying enzyme catalase. Interestingly, intracellular reactive oxygen species (ROS) were drastically reduced by treatment with noradrenaline, indicating that the neurotransmitter itself acted as an antioxidant. Prevention of oxidative stress was, however, independent of the glutathione antioxidant defense system. Chemical analogues of noradrenaline bearing two free hydroxyl groups in the ortho position of the aromatic ring (o-catechols), as well as o-catechol itself, mimicked the survival promoting effects of the neurotransmitter, suggesting that this diphenolic structure was critical for both neuroprotection and reduction of ROS production. Paradoxically, the autoxidation of noradrenaline and the ensuing production of quinone metabolites may be required for both effects, as the neurotransmitter was spontaneously and rapidly degraded over time in the culture medium. These results support the concept that central noradrenergic mechanisms have a neuroprotective role, perhaps in part by reducing oxidative stress.