Pharmacological interactions between serotonin and dopamine on behavior in the squirrel monkey

Area of Science:

• Neuroscience
• Pharmacology
• Behavioral Science

Background:

• Selective dopamine uptake inhibitors like GBR 12909 are crucial tools for studying dopamine's role in behavior.
• Understanding the interaction between different neurotransmitter systems, such as dopamine and serotonin, is key to explaining complex behavioral responses to drugs.

Purpose of the Study:

• To investigate the behavioral effects of GBR 12909, a selective dopamine transporter inhibitor, in squirrel monkeys.
• To examine the modulatory role of serotonin (5HT) system drugs on the behavioral effects of GBR 12909.
• To compare the pharmacological profile of GBR 12909 with that of cocaine.

Main Methods:

• Squirrel monkeys were trained on a fixed-interval schedule of stimulus termination and a second-order schedule of intravenous drug self-administration.
• The effects of GBR 12909 alone and in combination with selective serotonin reuptake inhibitors, a serotonin agonist, and a serotonin antagonist were assessed.
• The effects of dopamine agonists (quinpirole, apomorphine) alone and with a serotonin antagonist were also evaluated.

Main Results:

• GBR 12909 increased response rates on the fixed-interval schedule at intermediate doses, while the highest dose decreased them.
• Serotonin uptake inhibitors attenuated GBR 12909's stimulant effects, whereas a serotonin antagonist enhanced them.
• GBR 12909 supported self-administration, and a serotonin antagonist increased responding maintained by a high dose.

Conclusions:

• Serotonin (5HT) reliably modulates the behavioral effects of psychomotor stimulants with prominent dopaminergic actions.
• The findings suggest that GBR 12909's behavioral profile, particularly its interactions with serotonin drugs, resembles that of cocaine.
• This study reinforces the significant role of serotonin in regulating dopamine-mediated stimulant effects.