EN
Inhibition of monoamine transporters by a psychostimulant, cocaine, increases the monoamines availability at synaptic cleft and leads to the enhanced stimulation of monoaminergic postsynaptic receptors. G proteins represent the down-stream connectors from receptors to intracellular signalling. The aim of the study was to assess the expression of Gα(q), Gα(11) and Gα(12) mRNAs following reinstatement of cocaine-seeking behaviour in the prefrontal cortex (PFC) and the amygdala (AMY) of male Wistar rats using a “yoked” procedure and RT-PCR technique. We found that phases of cocaine-seeking behavior differently influenced the Gα subunits depending on the brain structure analyzed. Cocaine self-administered for 18 days induced a significant increase of mRNA levels of all Gα subunits (by ~23% for Gα12 and Gα11, and by 46% for Gαq vs yoked) in the PFC. After 10 days withdrawal from cocaine when no change in G proteins was observed, reinstatement induced by priming dose of the drug decreased G12 and Gq. The effect was more pronounced after combination of the cocaine with cue previously associated with cocaine self-administration and was noticed in G11 as well. In AMY, changes in the expression of Gα mRNAs induced by cocaine self-administration dependent on environmental cues paired with cocaine. Cocaine self-administration decreased (by ~24%) all G protein mRNAs while opposite effect was observed when cocaine self-administration was paired with cue stimulus. Withdrawal from cocaine induced 2-fold increase in mRNA level of three G proteins. On the contrary, the reinstatement induced by the cue decreased significantly Gα mRNAs to the same degree as did its combination with cocaine-priming. Our study provides the first evidence that alterations of G proteins mRNA expression can be conditioned by environmental stimuli paired with cocaine administration. Supported by statutory funds of the Institute of Pharmacology PAS.