Article Figures & Data
Figures
- Figure 1.
A–C, Behavioral responses (A) and fluctuations in mean levels of glutamate (B) and GABA (C) during intravenous cocaine self-administration. D, A typical response record for a rat with microdialysis probe implanted in the VTA. Glutamate levels in the VTA but not in the region dorsal (DC) or lateral (SN) to the VTA were significantly increased after the initiation of the self-administration session. The dotted vertical lines at time = 0 indicate the start of the self-administration session. The asterisk (*) indicates significant (p < 0.05) difference from baseline levels.
- Figure 2.
A–C, Behavioral responses (A) and fluctuations in mean levels of glutamate (B) and GABA (C) during extinction. Rats tested for the first time in extinction responded vigorously in the early minutes of the session but did not maintain responding thereafter; a typical response record is shown in D. E, Rats tested for the 13th time in extinction responded minimally. B, Glutamate levels in the VTA but not in the SN or DC groups were significantly increased during the early period of the first substitution session. No such increase was seen on the 13th extinction trial. The dotted vertical lines at time = 0 indicate the start of the self-administration session. The asterisk (*) indicates significant (p < 0.05) difference from baseline levels.
- Figure 3.
A–C, Behavioral responses (A) and fluctuations in mean levels of glutamate (B) and GABA (C) in various groups during yoked cocaine infusions. Significant increases in glutamate levels were seen in all groups of cocaine self-administration-trained rats. In order of responsiveness, the groups were as follows: cocaine-trained animals given yoked infusions in the absence of the lever they would normally press for the drug (lever withheld); cocaine-trained animals given yoked infusions with the lever inserted (lever inserted); animals trained similarly but in a different room and test chamber (novel room); a group that had 2 weeks of experience with yoked infusions before the day of testing (yoked history); a group of saline-trained animals given yoked cocaine infusions for the first time (cocaine naive). D, E, The active lever-press pattern of a typical executive animal and a rat from the lever-inserted group, respectively. The dotted vertical lines at time = 0 indicate the start of the self-administration session.
- Figure 4.
A, B, Fluctuations in mean VTA levels of glutamate (A) and GABA (B) in animals receiving yoked infusions (lever-withheld condition) in the presence (circles) or absence (squares) of TTX perfusion through the dialysis probe. TTX (0.1 μm) perfusion began 30 min before baseline sample collection and continued throughout the experiment. The control group data were from Figure 3. The vertical doted lines indicate the start of the yoked cocaine infusion testing.
- Figure 5.
Mean response rate during cocaine self-administration as a function of bilateral VTA perfusion of the ionotropic glutamate receptor antagonist Kyn or its vehicle (aCSF). A, B, Kyn was perfused 1 h before (A) or 1 h after (B) the beginning of the cocaine self-administration sessions. In A, three animals did not initiate responding normally at the beginning of the session; rather, they initiated 12, 14, and 23 min into the session. In B, three rats with 5 mm Kyn perfusion essentially quit responding after ∼1 h of accelerated lever pressing after onset of Kyn infusion. C, D, The active lever-press pattern of a typical rat from aCSF perfusion group and one from 5 mm Kyn group, respectively.
- Figure 6.
Mean response rate during extinction as a function of bilateral perfusions of various concentrations of the ionotropic glutamate receptor antagonists. Perfusions of antagonists were started 1 h before the beginning of the extinction testing and continued until the end of the experiment. A, The dose comparisons for the nonselective antagonist Kyn. B, The site comparisons at 0.1 mm Kyn perfusion. C, The effects of the NMDA-type selective antagonist AP-5 and the AMPA/kainate-type selective antagonist CNQX.
- Figure 7.
Probe placements. Colored lines indicate the location of the active portion of the dialysis membrane. Right, Unilateral placements for microdialysis collection. Left, Bilateral placements for reverse dialysis experiments. Green, VTA placements; blue, SN placements; red, DC placements. The number of lines for the VTA group is less than the number of animals because of overlap in the placements. Drawings were adapted from the atlas of Paxinos and Watson (1998). The numbers on the right side of the drawings indicate the distance (in millimeters) posterior to the bregma.
