Figure 4. Oestrous cycle-dependent fluctuations in VTA and NAc are mediated by dopaminergic signalling.

(a) Timeline of CPP experiments and paired fibre photometry recordings during choice test 24 h after the last conditioning session. (b) Schematic of recording experiments for VTA cell body recordings in TH-BAC-Cre mice, which were taken during the saline or cocaine pairing. (c) Representative Ca²⁺ imaging traces from male (left), oestrus female (middle) and dioestrus female (right) mice during saline and cocaine conditioning. (d) Cocaine reduces the amplitude of VTA Ca²⁺ events (two-way analysis of variance (ANOVA); F_{(1, 8)}=8.63, P<0.01; *P<0.05 as compared with saline). (e) Cocaine-induced amplitude reductions in activity were greater during oestrus (one-way ANOVA; F_{(2, 8)}=23.76; *P<0.05) when compared with males or dioestrus females. (f) Schematic of recording experiments for VTA cell body and terminal recordings in TH-BAC-Cre mice, which were taken during the choice test, 24 h after the last conditioning session. (g) Left: representative VTA Ca²⁺ activity trace during choice test demonstrating increases in activity preceding entry (dashed line) into the drug-paired (blue). (g) Right: the area under the curve (ΔF/F) of the spike in Ca²⁺ activity preceding cocaine-paired chamber entry was increased in oestrus-conditioned female mice (one-way ANOVA; F_{(2, 8)}=5.80, P<0.05; *P<0.05). (h) Left: representative NAc Ca²⁺ activity trace. (h) Right: the area under the curve (ΔF/F) of the spike in Ca²⁺ activity in NAc terminals preceding cocaine-paired chamber entry (one-way ANOVA; F_{(2, 8)}=4.50, P<0.05). (i) Left: heat maps of VTA-dopamine Ca²⁺ activity over time during successive entries (rows) into the cocaine-paired chamber across groups. (i) Right: averaged VTA-dopamine Ca²⁺ activity in a window around paired chamber entry. (j) Left: heat maps of NAc terminal-dopamine Ca²⁺ activity over time during successive entries. (j) Right: averaged NAc terminal-dopamine Ca²⁺ activity in a window around paired chamber entry. Data represented as mean±s.e.m.