Archival ReportA Methamphetamine Vaccine Attenuates Methamphetamine-Induced Disruptions in Thermoregulation and Activity in Rats
Section snippets
Experimental Design
There were two experiments in this investigation. Experiment 1 was an initial screen to determine which of three most promising candidate anti-METH vaccines from a previous study in mice (40) would confer effects consistent with the attenuation of METH’s impact in vivo in rats. Experiment 1 therefore assessed rectal temperature values under a high ambient temperature condition (TA = 27±1°C) to determine effects on METH-induced hyperthermia and locomotor activity as previously described 41, 42.
Experiment 1
Antibody Titers. An equilibrium dialysis assay was performed to normalize the results among MH2(R), MH6, and MH7 haptens. The MH6 and MH7 haptens produced similar binding constants (Kd = ∼25–30 nmol/L; Table 2) but the MH6 hapten produced two to three times more antibody (Figure 1). Although MH6 and MH2(R) produced similar levels of antibody, MH2(R) had much lower affinity than MH6 (Kd = ∼2.24 μmol/L). Specificity of MH6 antibodies for METH, AMPH, MDMA, and 4-MMC was assessed by equilibrium
Discussion
This study provides unequivocal evidence that active vaccination is capable of attenuating physiological and behavioral effects of METH, unlike prior attempts at active immunotherapy for METH 37, 38. It was shown that active vaccination attenuated METH-induced disruptions in thermoregulation (i.e., hyperthermia and hypothermia at 27°C and 23°C, respectively), wheel activity (experiment 1), and stereotypy (experiment 2) after the highest METH dose administered. The progression of psychomotor
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