Figure 4. Inhibition of GABA_B IPSCs by Cocaine Is Independently Mediated by 5HT_1B and CB1 Receptors.

(A) Inhibition of GABA_B IPSC by cocaine was largely occluded by the 5HT_1B receptor agonist sumatriptan (300 nM).

(B) The selective 5HT_1B receptor antagonist GR55562 (1 or 10 μM) suppressed the inhibition by cocaine.

(C) The inhibition by cocaine was completely abolished when CB1 and 5HT_1B receptors were blocked simultaneously.

(D) Serotonin-induced depression of GABA_B IPSC is independent of CB1Rs. Application of the 5HT_1B agonist sumatriptan, the selective serotonin reuptake inhibitor citalopram (10 μM), or the serotonin releaser fenfluramine (10 μM) all depressed GABA_B IPSCs to a similar level. However, this is unaffected by the CB1R antagonist AM251 (4 μM; F_(2,46) = 0.25, p = 0.77, two-way ANOVA). Scale bar, 100 ms, 10 pA.

(E) Pre-treatment with the selective DA transport inhibitor, GBR12935 (1 μM), does not occlude the inhibition of GABA_B IPSCs by cocaine.

(F) The DA-D₂ receptor antagonist sulpiride (5 μM) does not prevent the inhibition by cocaine.

(G) Summary the effect of cocaine on GABA_B IPSCs with different drug treatments (F_(5,51) = 12.83, p < 0.0001, one-way ANOVA; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 versus cocaine; ^#p < 0.05 versus GR55562; Bonferroni post hoc analysis). The complete elimination of the cocaine-induced inhibition of GABA_B IPSCs by CB1R and 5-HT_1B antagonism indicates that these effects are independent.