Chunk #21 — Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways
Over 90% of the neurons in the NAc are GABAergic medium spiny interneurons (Kemp and Powell, 1971); the genes involved in synthesizing, storing and retrieving GABA (γ-aminobutyric acid) are expressed in the NAc, along with ionotropic and metabotropic GABA receptors (Figure 5). Expression of the GABA-synthesizing enzymes (Gad65, Gad67), the vesicular inhibitory amino acid transmitter transporter (Viatt) and the plasma membrane transporters (Gat1, Gat3 and Gat4) rose in response to cocaine and withdrawal. The three Na+/Cl--dependent GABA transporters are expressed by astrocytes and retrieve GABA after secretion (Bolteus and Bordey, 2004; Schousboe et al., 2004; Beenhakker and Huguenard, 2010); neurons also express Gat1 (Schousboe et al., 2011). Levels of Gat4 were highest after Cocaine while levels of Gat1 were highest in Withdrawal. Multiple GABAA receptor subunits are expressed at similar levels; while some showed a sustained increase in expression (Gabrb2, Gabrb3, Gabrg3, Gabrq), Gabrb1 expression decreased in Withdrawal and Gabrd expression decreased after Cocaine but recovered in Withdrawal. Expression of GABAB receptor subunits (Gabbr1, Gabbr2) increased after Cocaine and increased further during Withdrawal.