Figure 1. Oestrus-conditioned female mice exhibit elevated CPP for cocaine and enhanced basal reward circuit function.

(a) Timeline of cocaine CPP experiments. (b) Representative heat maps of time spent in each area of the CPP chamber for male (left), oestrus-conditioned females (centre) and dioestrus-conditioned females (right). (c) Increased CPP in females was only observed in mice paired with cocaine conditioning during oestrus (one-way analysis of variance (ANOVA); F_{(2, 12)}=13.13, P<0.001; **P<0.01 oestrus versus dioestrus, ^##P<0.01 oestrus versus male). (d) Electrophysiological traces showing increased phasic activity of VTA dopamine neurons in oestrus females. In vivo single-unit electrophysiology of basal activity of putative VTA dopamine neurons identified increased: (e) firing rate (Kruskal–Wallis (KW) (χ²₍₂₎=11.76, P<0.005; *P<0.05, ^###P<0.001), (f) percentage of spikes within burst (one-way ANOVA F_{(2, 36)}=7.858, P<0.005; */^#P<0.05) and (g) burst length (KW (χ²₍₂₎=10.17, P<0.01; *P<0.05, ^###P<0.001) in only oestrus females when compared with males (#) or dioestrus females (*). (h) FSCV recordings of subsecond dopamine release in the NAc. (i) Current versus time plots (left) and colour plots showing the presence of dopamine after one pulse tonic stimulation, as indicated by its oxidation at +0.6 V and reduction at −0.2 V. (j) Current versus time plots showing increased dopamine release to increasing frequency of five pulse stimulations. (k) Group data showing enhanced NAc dopamine per one pulse tonic stimulation in oestrus females (one-way ANOVA; F_{(2, 6)}=11.57; *P<0.05, ^#P<0.05). (l) Phasic responsivity was increased in oestrus females (two-way ANOVA; F_{(6, 18)}=3.279, P<0.05; *P<0.05, ^#P<0.05). (m) Phasic responses represented as a percent of one pulse (tonic) release. Oestrus females exhibit increased dopamine release during phasic stimulations (two-way ANOVA; F_{(3, 14)}=9.079, P<0.05; *P<0.05, ^#P<0.05). *P<0.05, **P<0.01, ***P<0.001 oestrus versus dioestrus (unless otherwise noted); ^#P<0.05, ^##P<0.01 oestrus versus male. Data represented as mean±s.e.m.