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Rationale <p>A central component of substance use disorder is the maladaptive choice of the drug over natural reinforcers. Compared to other drugs of abuse, methamphetamine (METH) choice has received limited study.</p> Objective <p>We sought to characterize the role of intertrial interval on METH choice behavior.</p> Methods <p>We examined the choice of METH versus food, across multiple METH doses (0.05–0.2&#xa0;mg/kg/infusion), between male and female rats, employing a fixed ratio (FR1) reinforcement schedule with intertrial intervals (ITIs) of 20 and 600&#xa0;s. Rats learned to lever-press for either the METH or the food reinforcer during separate, alternating training sessions. Rats then underwent choice testing, where both levers were presented for 25 discreet trials per session. Lastly, under a progressive ratio (PR) schedule, breakpoints for METH and food were assessed during separate, alternating sessions.</p> Results <p>METH choice was substantially higher when using the 20&#xa0;s versus 600&#xa0;s ITI. When the 20&#xa0;s ITI was used, choice was dose- but not sex-dependent. When using the 600&#xa0;s ITI, choice was influenced by dose and sex, with female rats in the higher dose group choosing METH more than other groups. PR breakpoints were higher for METH than for food, and this effect was more pronounced among female rats. METH choice was positively correlated with the ratio of METH/food breakpoints.</p> Conclusion <p>Reinforcement schedule parameters, namely ITI, during discrete choice testing can markedly influence METH choice behavior; thus, this should be carefully considered during experiment design and selected based on overarching study aims.</p>

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Time to choose: impact of intertrial interval on selecting between methamphetamine and food reinforcement in male and female rats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月8日

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  • Marlaina R. Stocco,
  • Mari Purpura,
  • Philip A. Vieira,
  • Kira Wallquist,
  • Sijia Wang,
  • Julia Adams,
  • Karen K. Szumlinski,
  • Tod E. Kippin

摘要

Rationale

A central component of substance use disorder is the maladaptive choice of the drug over natural reinforcers. Compared to other drugs of abuse, methamphetamine (METH) choice has received limited study.

Objective

We sought to characterize the role of intertrial interval on METH choice behavior.

Methods

We examined the choice of METH versus food, across multiple METH doses (0.05–0.2 mg/kg/infusion), between male and female rats, employing a fixed ratio (FR1) reinforcement schedule with intertrial intervals (ITIs) of 20 and 600 s. Rats learned to lever-press for either the METH or the food reinforcer during separate, alternating training sessions. Rats then underwent choice testing, where both levers were presented for 25 discreet trials per session. Lastly, under a progressive ratio (PR) schedule, breakpoints for METH and food were assessed during separate, alternating sessions.

Results

METH choice was substantially higher when using the 20 s versus 600 s ITI. When the 20 s ITI was used, choice was dose- but not sex-dependent. When using the 600 s ITI, choice was influenced by dose and sex, with female rats in the higher dose group choosing METH more than other groups. PR breakpoints were higher for METH than for food, and this effect was more pronounced among female rats. METH choice was positively correlated with the ratio of METH/food breakpoints.

Conclusion

Reinforcement schedule parameters, namely ITI, during discrete choice testing can markedly influence METH choice behavior; thus, this should be carefully considered during experiment design and selected based on overarching study aims.