Self-administration of methamphetamine aerosol by male and female baboons

Abstract

The reinforcing efficacy of vaporized methamphetamine HCl (0.3 mg/kg) was determined in baboons with minimal previous drug exposure. A group of 8 adult male baboons was tested prior to a group of 7 adult female baboons. Baboons were initially trained to suck on a brass stem activating a pressure-sensitive relay (i.e., puff), to receive one M&M® candy. Five of the 8 males and 6 of the 7 females learned to activate the relay. 0.05 ml of 95% ethyl alcohol containing 0.3 mg/kg methamphetamine was vaporized and delivered to the mouth of the baboon after he/she completed 2 puffs; a single candy was given after an additional 5 puffs to ensure that baboons continued puffing after the aerosol entered their mouths. Puffing was recorded but not reinforced by candy or drug for 2 min after each aerosol delivery for males and 1 min for females. Males could earn 10 and females could earn 20 aerosol deliveries. Males made between 225 and 650 puffs each session. Females made between 200 and 400 puffs each session. When only candy and placebo aerosol were delivered the number of puffs decreased in all 6 females but increased in all 5 males. When candy was delivered without aerosol, puffing decreased in 4 of 5 males, but this manipulation was not tested in females. Methamphetamine aerosol delivery maintained lower rates of puffing behavior in females than males, but procedural differences weaken interpretation of this sex comparison. Although training non-human primates to inhale drug vapors is time consuming, if successful, their long lifespan could provide years of valuable data justifying further work with non-human primates using models of vaporized drug self-administration.

Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts

“…Similarly, voluntary oral exposure of METH showed no sex differences in METH intake, but female METH exposed mice showed increased locomotor activity compared to male mice ( Avila et al, 2021 ). Finally, a recent study investigating potential sex differences in baboons ( Foltin, 2018 ) is of special interest because studies of nonhuman primates are rather rare. In that study, the author investigated the reinforcing efficacy of vaporized methamphetamine HCl (0.3 mg/kg) in animals with minimal prior exposure to drugs.…”

Self-administration of inhaled delta-9-tetrahydrocannabinol and synthetic cannabinoids in non-human primates.

“…In that study, responding decreased for methamphetamine compared to vehicle in males whereas responding increased for methamphetamine compared to vehicle in most females. Here, responding exceeded vehicle for at least one dose of JWH-073 and HU-210 in 75% of the group (≥ 50% of males and females) suggesting that certain cannabinoids are more consistently reinforcing across sexes compared to methamphetamine (Foltin, 2018). In earlier studies of aerosolized heroin self-administration in rhesus monkeys, it was possible to initiate and maintain heroin self-administration in the absence of candy pairings (Evans et al, 2003; Foltin & Evans, 2001).…”

“…In the current study, self-administered aerosolized drug and vehicle were paired with candy following a progressive ratio procedure such that a candy was paired with the 1st, 2nd, 5th, 9th, 14 th , and 20th aerosol deliveries; candy was not paired with subsequent aerosol deliveries. This procedure was similar to an earlier study in baboons assessing the reinforcing effects of aerosolized methamphetamine where each delivery was paired with a candy (Foltin, 2018). In that study, responding decreased for methamphetamine compared to vehicle in males whereas responding increased for methamphetamine compared to vehicle in most females.…”

“…A maximum of six candies was delivered per session with no candies delivered after the 20th aerosol delivery. This method was similar to earlier studies that used candy reinforcers to improve training of puffing behavior needed for smoked or aerosolized drug self-administration (i.e., Foltin, 2018;Pieper & Cole, 1973). Schedule contingencies were controlled by customized software (Eureka Software, Cary, NC) running on two Macintosh 610 computers (Cupertino, CA) located in an adjacent area.…”

“…Intrapulmonary heroin self-administration was also assessed as a positive control (Foltin & Evans, 2001). Earlier studies of aerosolized drug self-administration in non-human primates revealed sex-dependent effects with greater drug-reinforced responding in females (Foltin, 2018; Foltin & Evans, 2001). With respect to CB1 receptor agonist effects, female rodents are more sensitive to a range of CB1 receptor agonist outcomes compared to males including their abuse-related effects (i.e., Cooper & Craft, 2018), an effect that extends to humans (Cooper & Haney, 2014).…”