Methamphetamine

After adjustment to the ACF for 7 days, guinea pigs were randomly assigned to six study groups for subsequent treatment with one of the following: (a) phosphate buffered saline, herein denoted as saline), (b) SKF38393, dopamine D1 receptor (D1R) agonist, (c) SCH23390, D1R antagonist, (d) sulpiride, the dopamine D2 receptor (D2R) antagonist, (e) low-dose Methamphetamine, the mixed monoaminergic indirect agonist, or (f) high dose Methamphetamine. To make stock solutions, 10 mg SCH23390 or 20 mg sulpiride were first dissolved in 0.5 ml dimethyl sulfoxide (DMSO) and then made to final volume by adding 0.5 ml saline, respectively. The stock solutions were subsequently diluted with saline to provide drug concentrations of either 0.25 mg/kg SCH23390 or 1.0 mg/kg sulpiride that were administered to guinea pigs. Thus, the dilution factor for DMSO in the final 1.0 ml injections given to animals ranged between 1:20 and 1:40 for DMSO which corresponds to 0.0125 μM – 0.025 μM. We have found that application of these DMSO concentrations do not affect synaptic transmission (data not shown). Methamphetamine, sulpiride, DMSO and phosphate buffered tablets were obtained from Sigma-Aldrich (St. Louis, MO), whereas SCH23390 was acquired from Tocris (Ellisville, MO).

The methamphetamine (Sigma-Aldrich) was dissolved in 0.9% physiological saline and sterile filtered through a 0.22μm filter (ThermoScientific). The drug reinforcer was administered in doses of 0.25, 0.5, or 1.0 mg/kg IV in a volume of 0.1 ml over a period of 4.3 s. The selected range of doses was chosen to mimic aspects of human use on a dose/body weight basis and to be comparable to those reported for locomotor activation in rats following IV administration of the drug (e.g., Rivière et al., 1999 (link); Segal and Kuczenski, 2006 ). The selection of doses that produce locomotor activation was based on the observation that the locomotor response to psychomotor stimulants, including methamphetamine, has been shown to be predictive of drug reward as measured by subsequent IV self-administration (e.g., Piazza et al., 1989 (link), 1990 (link); Vezina, 2004 (link); Gancarz et al., 2011 (link)).

HIV-1gp120 MN (product #1021-2) was purchased from Immunodiagnostics, Inc. (Woburn, MA). Aliquots of gp120 were kept as 100nM stock solution at −80°C. The stock solution was diluted to desired concentrations with artificial cerebrospinal fluid (ACSF) 2–5 min before test. (+)methamphetamine was purchased from Sigma (St. Louis, MO, Cat # M-8750) with DEA license # RX0374974. All chemicals, unless otherwise specified, were from Sigma.

Methamphetamine was purchased from Sigma-Aldrich (St. Louis, MO). α-Pyrrolidinopentiophenone (α-PVP) was synthesized in house using standard synthetic procedures. It was formulated as recrystalized salt and was > 97% pure. The purity was assessed by several analytical techniques including carbon, hydrogen, nitrogen (CHN) combustion analysis and proton nuclear magnetic resonance spectroscopy. Compounds were dissolved in sterile saline USP (Butler Schein, Dublin, OH) for injection, and in 50% propylene glycol + 50% vegetable glycerin (Fisher Scientific, Pittsburg, PA; J.T. Baker, Center Valley, PA) for vaporization, a vehicle that is commonly used in e-cigarettes. Injected doses are expressed as mg/kg of the salt, and were injected intraperitoneally (i.p.) at a volume of 10 ml/kg. Vapor exposure concentrations are expressed as mg/ml of the salt in the e-cigarette tank, and are not representative of the actual amount of drug inhaled. Sterile saline vehicle and 50% propylene glycol + 50% glycerin vehicle were used as comparisons for injected and vaporized compounds, respectively.