Effects of Pargyline and Para-Chlorophenylalanine on Mouse Social Behavior

Background:  Impaired social behavior is a core symptom of autism that also appears in other psychiatric disorders like schizophrenia, bipolar disorder and depression. It has proven to be among the most treatment-resistant of psychiatric illness symptoms. Serotonin (5-HT) is a monoamine neurotransmitter that regulates mood balance in the brain, it is also a strong shaper of social behavior. For example in some patients and in mice sociability deficits in behavior tests worsen with decreases in 5-HT availability, but improve following administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine, which enhances 5-HT neurotransmission. 

Objectives:  The purpose of this study was to determine if increasing serotonin availability in the brain would correspond with improvements in sociability. Conversely we predicted that reducing serotonin availability in the brain would worsen sociability in either innately gregarious or socially deficient mice.  

Methods:  To test this hypothesis, we performed social interaction, social novelty, locomotor and repetitive behavioral tests on BTBR mice, a socially deficient s inbred strain, and C57BL/6 mice, which display normal social behaviors. Before testing, adult males of both strains were given either a single injection of 100 mg/kg pargyline, a monoamine oxygenase inhibitor, to block the metabolic breakdown of 5-HT in the brain, or 300 mg/kg over 3 days of para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor to block 5-HT synthesis in the brain.  Controls were treated with vehicle on the same schedule with the drug treatments. The behavioral tests employed were mouse three-chamber sociability and marble burying as an index of restrictive repetitive behavior.

Results:  We observed in social interaction preference tests that PCPA treatment enhanced PCPA increased locomotor activity in C57BL/6, but not BTBR mice. More critically PCPA reduced social interaction preference in both strains, with little effect on social novelty preference.  On the other hand, pargyline enhanced social interaction preference in C57BL/6 and social novelty preference in both strains. Marble burying was unchanged by either PCPA or pargyline treatments.

Conclusions: Findings from our study demonstrate that pargyline likely induced increases in brain serotonin concentrations that enhanced social behavior in both socially impaired mice, and normal mice.  Conversely they also show that PCPA induced-decreases in available brain serotonin generally suppressed mouse sociability.  Overall, these findings lend further support to the hypothesis that sociability is shaped by central 5-HT availability.