Abstract Title

Modafinil as a Pharmaceutical Therapy for Cocaine Withdrawal

Presenter Name

Daniel L. McMahan

RAD Assignment Number

2101

Abstract

Purpose: Modafinil has been proposed as a possible pharmaceutical adjunct therapy for cocaine withdrawal. This study tested Modafinil’s interaction with cocaine to determine its usefulness in a clinical setting.

Materials and Methods: This study used a total of 48 mice separated into the following groups of 8 mice each:

Group 1 – Dose 1 [5 mg Modafinil] + Dose 2 [Vehicle (Saline)]

Group 2 – Dose 1 [10 mg Modafinil] + Dose 2 [Vehicle (Saline)]

Group 3 – Dose 1 [5 mg Modafinil] + Dose 2 [8 mg Cocaine]

Group 4 – Dose 1 [10 mg Modafinil] + Dose 2 [8 mg Cocaine]

Group 5 – Dose 1 [Vehicle (Methyl Cellulose)] + Dose 2 [8 mg Cocaine]

Group 6 – Dose 1 [Vehicle (Methyl Cellulose)] + Dose 2 [Vehicle (Saline)]

*Each dose contained 0.33 mL of bracketed [] solution.

All Modafinil drug preparations were made by mixing Modafinil with methyl cellulose. A 25G needle was used to inject “Dose 1” (Modafinil drug preparation) into the left-lower abdominal quadrant of Groups 1-4. The same gauge needle was also used for injecting “Dose 1” to Groups 5-6; however, these doses excluded Modafinil and only contained methyl cellulose.

All Cocaine drug preparations were made by mixing Cocaine with normal saline. A 28G needle was used to inject “Dose 2” (Cocaine drug preparation) into a different location in the left-lower abdominal quadrant of Groups 3-5. The same gauge needle was also used for injecting “Dose 2” to Groups 1, 2, 6; however, these doses excluded Cocaine and only contained normal saline.

All groups of mice were given “Dose 1” and allowed to wait for 15 minutes (“pretreatment time”). After this pretreatment time, all groups of mice were administered “Dose 2” and immediately placed in separate locomotor activity (“LMA”) boxes for 120 minutes. The data was obtained from said LMA boxes and analyzed to determine the effects of the above various concentrations of drugs on the mice’ locomotor activity.

Summary: The average horizontal ambulation count for Group 6 was 2,586. This was used as a baseline for judging the effects of the various drug combinations. The average horizontal ambulation count for the remaining groups was as follows: Group 1 – 3,265; Group 2 – 3,741; Group 3 – 4,436; Group 4 – 5,508; Group 5 – 3,434. In summary, Modafinil alone increased the locomotor activity above baseline in proportion to its dosage. When cocaine was subsequently added, the ambulation count grew even higher.

Conclusions: This study suggests that Modafinil and cocaine act via a common pathway. It is known that Modafinil is an atypical inhibitor of the dopamine transporter (DAT) and cocaine is a typical inhibitor of DAT. It is hypothesized that this pathway is responsible for the increased locomotor activity observed in this study. The results obtained suggest that Modafinil and cocaine in combination produce an additive effect on locomotor activity in mice. Increasing the Modafinil dosage from 5-10mg, while leaving cocaine constant at 8 mg, produced an increased ambulation count. Further testing must be done in order to elucidate whether or not cocaine and Modafinil truly act via a common pathway. It is suggested that repeating this study by using a 20 mg cocaine dosage would effectively answer this question. Prior research suggests that administering >20mg cocaine to mice effectively decreases locomotor activity; therefore, progressive decreases in locomotor activity when administering progressive increases in Modafinil in combination with a constant 20 mg dose of cocaine would suggest that Modafinil acts via a common pathway. This research would need to be conducted before a judgment could be made regarding Modafinil’s value in treating cocaine withdrawal.

Research Area

Pharmacology

Presentation Type

Poster

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Modafinil as a Pharmaceutical Therapy for Cocaine Withdrawal

Purpose: Modafinil has been proposed as a possible pharmaceutical adjunct therapy for cocaine withdrawal. This study tested Modafinil’s interaction with cocaine to determine its usefulness in a clinical setting.

Materials and Methods: This study used a total of 48 mice separated into the following groups of 8 mice each:

Group 1 – Dose 1 [5 mg Modafinil] + Dose 2 [Vehicle (Saline)]

Group 2 – Dose 1 [10 mg Modafinil] + Dose 2 [Vehicle (Saline)]

Group 3 – Dose 1 [5 mg Modafinil] + Dose 2 [8 mg Cocaine]

Group 4 – Dose 1 [10 mg Modafinil] + Dose 2 [8 mg Cocaine]

Group 5 – Dose 1 [Vehicle (Methyl Cellulose)] + Dose 2 [8 mg Cocaine]

Group 6 – Dose 1 [Vehicle (Methyl Cellulose)] + Dose 2 [Vehicle (Saline)]

*Each dose contained 0.33 mL of bracketed [] solution.

All Modafinil drug preparations were made by mixing Modafinil with methyl cellulose. A 25G needle was used to inject “Dose 1” (Modafinil drug preparation) into the left-lower abdominal quadrant of Groups 1-4. The same gauge needle was also used for injecting “Dose 1” to Groups 5-6; however, these doses excluded Modafinil and only contained methyl cellulose.

All Cocaine drug preparations were made by mixing Cocaine with normal saline. A 28G needle was used to inject “Dose 2” (Cocaine drug preparation) into a different location in the left-lower abdominal quadrant of Groups 3-5. The same gauge needle was also used for injecting “Dose 2” to Groups 1, 2, 6; however, these doses excluded Cocaine and only contained normal saline.

All groups of mice were given “Dose 1” and allowed to wait for 15 minutes (“pretreatment time”). After this pretreatment time, all groups of mice were administered “Dose 2” and immediately placed in separate locomotor activity (“LMA”) boxes for 120 minutes. The data was obtained from said LMA boxes and analyzed to determine the effects of the above various concentrations of drugs on the mice’ locomotor activity.

Summary: The average horizontal ambulation count for Group 6 was 2,586. This was used as a baseline for judging the effects of the various drug combinations. The average horizontal ambulation count for the remaining groups was as follows: Group 1 – 3,265; Group 2 – 3,741; Group 3 – 4,436; Group 4 – 5,508; Group 5 – 3,434. In summary, Modafinil alone increased the locomotor activity above baseline in proportion to its dosage. When cocaine was subsequently added, the ambulation count grew even higher.

Conclusions: This study suggests that Modafinil and cocaine act via a common pathway. It is known that Modafinil is an atypical inhibitor of the dopamine transporter (DAT) and cocaine is a typical inhibitor of DAT. It is hypothesized that this pathway is responsible for the increased locomotor activity observed in this study. The results obtained suggest that Modafinil and cocaine in combination produce an additive effect on locomotor activity in mice. Increasing the Modafinil dosage from 5-10mg, while leaving cocaine constant at 8 mg, produced an increased ambulation count. Further testing must be done in order to elucidate whether or not cocaine and Modafinil truly act via a common pathway. It is suggested that repeating this study by using a 20 mg cocaine dosage would effectively answer this question. Prior research suggests that administering >20mg cocaine to mice effectively decreases locomotor activity; therefore, progressive decreases in locomotor activity when administering progressive increases in Modafinil in combination with a constant 20 mg dose of cocaine would suggest that Modafinil acts via a common pathway. This research would need to be conducted before a judgment could be made regarding Modafinil’s value in treating cocaine withdrawal.