title: Dynamic changes in extracellular release of GABA and glutamate in the lateral septum during social play behavior in juvenile rats: Implications for sex-specific regulation of social play behavior.
abstract: Social play is a motivated and rewarding behavior that is displayed by nearly all mammals and peaks in the juvenile period. Moreover, social play is essential for the development of social skills and is impaired in social disorders like autism. We recently showed that the lateral septum (LS) is involved in the regulation of social play behavior in juvenile male and female rats. The LS is largely modulated by GABA and glutamate neurotransmission, but their role in social play behavior is unknown. Here, we determined whether social play behavior is associated with changes in the extracellular release of GABA and glutamate in the LS and to what extent such changes modulate social play behavior in male and female juvenile rats. Using intracerebral microdialysis in freely behaving rats, we found no sex difference in extracellular GABA concentrations, but extracellular glutamate concentrations are higher in males than in females under baseline conditions and during social play. This resulted in a higher glutamate/GABA concentration ratio in males vs. females and thus, an excitatory predominance in the LS of males. Furthermore, social play behavior in both sexes is associated with significant increases in extracellular release of GABA and glutamate in the LS. Pharmacological blockade of GABA-A receptors in the LS with bicuculline (100 ng/0.5 μl, 250 ng/0.5 μl) dose-dependently decreased the duration of social play behavior in both sexes. In contrast, pharmacological blockade of ionotropic glutamate receptors (NMDA and AMPA/kainate receptors) in the LS with AP-5+CNQX (2mM+0.4mM/0.5 μl, 30 mM+3mM/0.5 μl) dose-dependently decreased the duration of social play behavior in females, but did not alter social play behavior in males. Together, these data suggest a role for GABA neurotransmission in the LS in the regulation of juvenile social play behavior in both sexes, while glutamate neurotransmission in the LS is involved in the sex-specific regulation of juvenile social play behavior.
authors: Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA. Electronic address: remco.bredewold@bc.edu.
authors: R
authors: R
authors: Bredewold
authors: Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA.
authors: J K
authors: JK
authors: Schiavo
authors: BrainsOnline, South San Francisco, CA, USA.
authors: M
authors: M
authors: van der Hart
authors: Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA.
authors: M
authors: M
authors: Verreij
authors: Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA.
authors: A H
authors: AH
authors: Veenema
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D017551:Microdialysis; D010988:Play and Playthings / Q000523:psychology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000378:metabolism*; D012727:Sex Characteristics; D012919:Social Behavior; D053719:Tandem Mass Spectrometry; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: GABA; glutamate; lateral septum; microdialysis; sex difference; social play