Hippocampal group III mGlu receptor mRNA levels are not altered in specific mouse models of stress, depression and antidepressant action.
The neurotransmitter glutamate is increasingly being implicated as playing a role in the molecular pathology underlying depression. The group III family of metabotropic glutamate (mGlu) receptors (mGlu(4,) mGlu(7) and mGlu(8) receptors) remains the most poorly investigated of all glutamate receptors in this regard, despite early research efforts showing that they may be major players in stress-induced pathology, genetic vulnerability to the onset of depression and in the action of pharmacotherapies. To redress this deficit, we investigated whether the mRNA levels of the group III mGlu receptors display sensitivity to the preclinical stress models' chronic immobilisation stress (CIS) in BALB/c mice and chronic social defeat in BALB/c and C57BL/6j mice. We also investigated the potential of the mood stabiliser lithium to reverse any stress-induced alterations to expression levels of the group III mGlu receptors. Furthermore, we investigated if changes to hippocampal group III mGlu receptors are involved in the augmentation strategy of administering lithium in conjunction with the tricyclic antidepressant desipramine using BALB/c mice. Finally, we investigated whether differences in hippocampal group III mGlu receptors exist between the non-helpless NH/Rouen mouse line and the helpless H/Rouen line. We found no changes to hippocampal group III mGlu receptor expression in any of the stress models investigated, the H/Rouen mouse genetic model of depression or due to pharmacological treatment. This indicates that these receptors may not be involved in the manifestation of behavioural and physiological changes observed in these models and furthermore, may not contribute to the therapeutic mechanisms of the above mentioned pharmacotherapies.
School of Pharmacy, University College Cork, Ireland.
Richard M
RM
O'Connor
Matteo M
MM
Pusceddu
Olivia F
OF
O'Leary
Helene M
HM
Savignac
Javier A
JA
Bravo
Malika
M
El Yacoubi
Jean-Marie
JM
Vaugeois
Timothy G
TG
Dinan
John F
JF
Cryan
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003863:Depression / Q000235:genetics*; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012149:Restraint, Physical / Q000523:psychology; D013315:Stress, Psychological / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D000928:Antidepressive Agents; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D018021:Lithium Chloride; D003891:Desipramine