TL neuro

June 7, 2015

Active vaccination against methamphetamine slows acquisition of self-administration

Filed under: Methamphetamine, Vaccines — mtaffe @ 7:01 pm

The following has been recently accepted for publication:

Miller, M.L., Aarde, S.M., Moreno, A.Y., Creehan, K.M., Janda, K.D. and Taffe, M.A Effects of active anti-methamphetamine vaccination on intravenous self-administration in rats. Drug Alcohol Depend, 2015, 153:29-36 [Publisher Site]

In this new paper we follow up on our first finding that a anti-methamphetamine conjugate vaccine (referred to as the MH6-KLH conjugate) changes locomotor activity and body temperature responses to methamphetamine [Miller et al, 2013; blog post]. The new study uses an intravenous self-administration paradigm in rats to determine if MH6-KLH vaccination is capable of altering voluntary dosing with methamphetamine. The rats are surgically implanted with indwelling venous catheters which may be attached to a micro-pump during testing sessions. Upon making a press on the drug-associated lever a small infusion of drug is delivered. Over successive (daily) testing sessions, if the amount of drug-associated lever pressing increases while responses on the other lever stay at low levels, this can be interpreted as the rats having learned that the drug is pleasurable. They also tend to express their satiety point in terms of relatively stable asymptotic levels of intake after about 10-15 sessions.

Figure1AThe main takeaway message from this study is that we are the first to show an attenuation of voluntary methamphetamine (MA) intake by means of active vaccination. In this figure, we show the percentage of rats in the MH6-KLH and KLH-only (control) groups who self-administered at least 11 infusions (0.1 mg/kg/inf) on two consecutive days. This acquisition criterion is arbitrary but using a cutoff of a few more or slightly fewer infusions makes little difference in the overall picture. In this case a survival analysis identified significantly delayed acquisition in the MH6-KLH vaccinated group. As we write in the paper

The delay in acquisition was substantial, with less than 17% of the vaccinated group reaching acquisition criteria after 7 sessions compared with 75% of controls. Furthermore, only 66% of the MH6-KLH-vaccinated rats compared with 100% of the controls reached acquisition criteria by 13 sessions of training.

Whether these findings reflect a real-world impact and significance, well, that is a matter of debate and additional investigation. Our position is that many people experience various psychoactive drugs and never go on to develop lasting addiction and/or liability for compulsive use. Some of these trajectories include the pattern of trying the drug once or a few times and deciding it doesn’t do much for the individual. The largest difference in the percent of animals opting not to take substantial amounts of MA in a daily session came after 7 chances. In our model, rats continue to be offered MA and indeed are given a priming injection if they haven’t made a response in 30 min. This was done to bias the study for complete population acquisition, at least in the control group. Real world users, of course, often make choices which prevent them from even having the opportunity to try MA again if they find it unpalatable after the first few exposures.

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These studies are funded by NIH Grant R01 DA024705

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