Fig 1.
Scheme of the experimental design.
From the fourth session the C+E group received ethanol along with cocaine.
Fig 2.
Percentage of rats that met the acquisition criterion according to treatment and sex.
The asterisk shows significant differences between male and female rats administered C+E. In the first three sessions (-3 to -1) the C+E rats received cocaine alone (1 mg/kg/bodyweight/injection) and they were not assessed for the acquisition criterion. None of the rats in the saline group fulfilled the conditions of acquisition.
Fig 3.
Maintenance of Coc and C+E self-administration.
Mean (±SEM) of the response rate/time (lever presses per minute). The C+E and Coc rats follow a similar pattern of escalation. No session-sex interaction was detected.
Fig 4.
Optimization of L-Tyr, L-Phe, L-Val and L-Asp assessment.
(A) Electropherograms of the optimization of the concentration of β-CD in running buffer. (B) Detail of the separation achieved with 4 mM β-CD: (C) Superposition of electropherograms: red, plasma sample; black, mix of 21 amino acids (100 mM) and blue, L-Tyr, L-Phe, L-Iso, L-Leu and L-Val. (0.5 mM).
Fig 5.
Plasma concentration of L-Tyr according treatment and sex.
Mean (±SEM) of L-Tyr. Effects of Sex, reflected by the higher concentration in male rats, and Treatment were found (C+E vs. Coc; C+E vs. Sal). * P<0.05; ** P<0.001.
Table 1.
Effect of self-administration of cocaine and C+E on plasma amino acid concentrations (μM/L).
Fig 6.
Effects of cocaine and C+E on amino acids molar ratios.
(A) Mean (±SEM) of the BCAA/L-Tyr molar ratio. Effects by Sex, Treatment and their interaction were significant. The ratio was higher in female Coc rats and even higher in those that received C+E. (B) Mean (±SEM) of the L-Tyr/L-Phe molar ratio, where a Treatment effect (C+E vs. Sal) was found. Sex differences were also seen, with a smaller ratio in females with Coc and even lower with C+E compared to the males. * p<0.05; ** p<0.001.
Table 2.
Effect of self-administration of cocaine and C+E on plasma amino acid molar ratios.