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Reciprocal Substitution Between Methamphetamine and Heroin in Terms of Reinforcement Effects in Rats - PubMed

  • ️Wed Jan 01 2020

Reciprocal Substitution Between Methamphetamine and Heroin in Terms of Reinforcement Effects in Rats

Di-Sen Mei et al. Front Psychiatry. 2020.

Abstract

Heroin and methamphetamine are both popular illicit drugs in China. Previous clinical data showed that habitual users of either heroin or methamphetamine abuse the other drug for substitution in case of unavailability of their preferred drug. The present study aimed to observe whether heroin can substitute the methamphetamine reinforcement effect in rats, and vice versa. Rats were trained to self-administer heroin or methamphetamine (both 50 μg/kg/infusion) under an FR1 reinforcing schedule for 10 days. After having extracted the dose-effect curve of the two drugs, we administered methamphetamine at different doses (12.5-200 μg/kg/infusion) to replace heroin during the period of self-administration, and vice versa. The heroin dose-effect curve showed an inverted U-shaped trend, and the total intake dose of heroin significantly increased when the training dose increased from 50 to 100 or 200 μg/kg/infusion. Following replacement with methamphetamine, the total dose-effect curve shifted leftwards and upwards. By contrast, although the dose-effect curve of methamphetamine also showed an inverted U-shaped trend, the total dose of methamphetamine significantly decreased when the training dose decreased from 50 to 25 μg/kg/infusion; conversely, when the methamphetamine training dose increased, the total dose did not change significantly. The total dose-effect curve shifted rightwards after heroin was substituted with methamphetamine. Although heroin and methamphetamine had their own independent reward effects, low doses of methamphetamine can replace the heroin reward effect, while high doses of heroin can replace the methamphetamine reward effect. These results demonstrated that heroin and methamphetamine can substitute each other in terms of reinforcement effects in rats.

Keywords: addiction; amphetamine; conditioning reward; drug abuse; opiate.

Copyright © 2020 Mei, Cai, Wang, Ma, Liu, Zhou and Xu.

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Figures

Figure 1
Figure 1

Dose–effect response in heroin self-administration. Rats (n = 19) were successfully trained to self-administer heroin 4 h/d under an FR1 reinforcing schedule within 10 days (A). When the heroin trained rats were tested in different dose (5 μg/kg/infusion–200 μg/kg/infusion) of heroin to self-administer 4 h in the following days (n=6-10/group). The active pokes and the infusions were changed and showed an inverted U trend, whose peak likely being 25 μg/kg/infusion (B, C). Rats took more heroin when doses increased to wither 100 or 200 μg/kg/infusion and less heroin intake when doses highly decreased to either 5 or 12.5 μg/kg/infusion, but maintained the total dose unchanged following the dose decreased to lower at 25 μg/kg/infusion (D). **P < 0.01, compared to 25 μg/kg/infusion; # P < 0.05, ## P < 0.01, compared to 50 μg/kg/infusion. Error bars = SEM.

Figure 2
Figure 2

MA substituted for heroin reinforcement. As substitution with different dose of MA to self-administer 4 h in heroin trained rats (n=9-10/group), only dose of 50 μg/kg/infusion of MA significantly increased the active pokes and the lower doses of 12.5, 25, 50 μg/kg/infusion of MA increased the infusions (A, B). The total dose significantly increased above the training MA dose of 50 μg/kg/infusion, and 25 μg/kg/infusion could equally instead of 50 μg/kg/infusion heroin self-administration at total dose (C).The total dose–effect curve of MA replacement showed shifted leftward and upward compared to the total dose–effect curve of heroin (D). *P < 0.05, **P < 0.01, compared to 50 μg/kg/infusion heroin. Error bars = SEM.

Figure 3
Figure 3

Dose–effect response in MA self-administration. Rats (n=16) were successfully trained to self-administer MA 4 h/day under an FR1 reinforcing schedule within 10 days (A). When the MA trained rats were tested in different dose (25 μg/kg/infusion–200 μg/kg/infusion) of MA to self-administer 4 h in the following days (n=7-8/group). The active pokes and the infusions were changed and showed an inverted U trend. The number of active pokes and infusions decreased significantly at high MA doses (100 or 200 μg/kg/infusion) compared to 50 μg/kg/infusion doses (B, C). Rat took less MA when dose decreased to 25 μg/kg/infusion, but maintain the total dose unchanged as dose increased (100, 200 μg/kg/infusion) (D). **P < 0.01, compared to 50 μg/kg/infusion MA. Error bars = SEM.

Figure 4
Figure 4

Heroin substituted for MA reinforcement. As substitution with different dose of heroin to self-administer 4 h in MA trained rats (n = 5–6/group), the higher doses (50, 200 μg/kg/infusion) of heroin significantly decreased the active pokes and the infusions (A, B). The total intake dose of heroin significantly decreased at 50 μg/kg/infusion or below when replaced with heroin, and 200 μg/kg/infusion heroin could equally instead of 50 μg/kg/infusion MA self-administration at total dose (C). The total dose–effect curve of heroin replacement showed shifted rightward and downward compared to the total dose–effect curve of MA (D) *P < 0.05, **P < 0.01, compared to 50 μg/kg/infusion MA. Error bars = SEM.

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