GPR55 activation prevents amphetamine-induced conditioned place preference and decrease the amphetamine-stimulated...

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Psychostimulant-induced neuroinflammation in the Central Nervous System (CNS) is implicated in drug addiction.
• The ventral hippocampus (vHp) is a key brain region in the reward pathway and expresses G protein-coupled receptor 55 (GPR55).
• GPR55's role in modulating neuroinflammation and its impact on psychostimulant consumption remain unclear.

Purpose of the Study:

• To investigate if activating GPR55 in the vHp can prevent amphetamine (AMPH)-induced inflammation and conditioned place preference (A-CPP).

Main Methods:

• Wistar rats underwent A-CPP induction with AMPH (5 mg/kg).
• The vHp was analyzed for IL-1β and IL-6 expression using RT-PCR, Western blot, and immunofluorescence.
• GPR55 agonist (LPI) or antagonist (CID) was infused into the vHp.
• Lipopolysaccharide (LPS) was used to induce inflammation and its effects were assessed.

Main Results:

• AMPH induced A-CPP and increased IL-1β and IL-6 levels in the vHp.
• Ventral hippocampus GPR55 activation with LPI prevented A-CPP and reduced AMPH-induced IL-1β.
• LPS administration exacerbated A-CPP and neuroinflammation, which was reversed by LPI.
• LPS increased markers of glial activation (CD68, Iba1) and intermediate filaments (GFAP, vimentin).

Conclusions:

• GPR55 activation in the ventral hippocampus mitigates the rewarding effects of amphetamine.
• Ventral hippocampus GPR55 activation reduces neuroinflammation associated with psychostimulant use.
• Targeting vHp GPR55 may offer a novel therapeutic strategy for psychostimulant addiction by interfering with pro-inflammatory responses.