Figure 5. Enhancing VTA dopamine activity in dioestrus females increases cocaine reward processing.

(a) Schematic of VTA firing through the oestrous cycle (top); experimental design using excitatory DREADDS (hM3Dq) expressed exclusively in dopamine neurons using TH-BAC-Cre mice to increase VTA dopamine activity (bottom). (b) Representative FSCV current versus time plots showing dopamine release to increasing frequency stimulations during oestrus, dioestrus or in males on the second day of vehicle or CNO injections. (c) Group data demonstrate enhanced dopamine per stimulation in dioestrus females and males that were given CNO to enhance VTA firing rates (one-way analysis of variance (ANOVA); F_{(5, 12)}=3.78, P<0.05; *P<0.05). (d) Phasic responsivity was increased in dioestrus females and males given CNO (two-way ANOVA; F_{(5, 8)}=3.93, P<0.05; *P<0.05. (e) Colour plots showing the presence of dopamine, as indicated by its oxidation at +0.6 V and reduction at −0.2 V, and the effects of bath application of 1, 3, 10 and 30 μM cocaine in each group. (f) Concentration–response curves showing that cocaine potency is increased in oestrus females and dioestrus females that were given CNO as compared with dioestrus controls. (g) K_i values showing that the affinity of cocaine for DAT is increased in dioestrus females and males given CNO (one-way ANOVA; F_{(5, 12)}=3.89, P<0.05; *P<0.05). (h) Schematic of CPP experiments with CNO injections. (i) Increased CPP in male and dioestrus females with CNO+DREADDs to increase VTA firing (one-way ANOVA; F_{(5, 12)}=3.78, P<0.05; *P<0.05 versus dioestrus). Data represented as mean±s.e.m.