160 T 140 - 120 - 3 100 - <p 80 - 0) 6 0 -
0
20
- - 600 400 .500 300 100 200 0Taurine-efflux (fmol)
Fig. 19 c, d Linear regression between glutamate- and taurine-efflux in response to infusions only in control and BLA-lesioned animals respectively. Both groups showed significant positive correlations between the release of the two amino acids (r=0.65, p< 0.001) control animals (Fig. 19c) and (r=0.51, p<0.01) lesioned animals (Fig. 19d). Control animals and lesioned animals also showed significant linear relationships (b=0.12+0.024, p < 0.001) and(b=0.12+0.04, p<0.01) respectively.
Taurine and glutamate regression coefficient: Intra-Nacc
Figure 19c and 19d show scatterplots of the extracellular concentration of Trn and Glu release following intra-Nacc infusion in sham-operated and BLA-lesioned animals respectively. Taurine and Glu release was significantly conelated in sham-
operated control animals (r=0.65, p<0.001) and BLA-lesioned animals (r=0.51, p<0.01) and there was also a significant linear relationship between the amino acids in both the control and lesioned groups (b=0.12+0.024, p<0.001) and
(b=0.12+0.04, p<0.01) respectively.
Summary
Relative to controls, BLA-lesioned animals were impaired in their basal and cocaine-induced Glu-efflux. However, these lesioned animals did not differ
significantly from controls in their basal or cocaine-induced DA- and Tm-efflux, and both groups also responded similarly to intra-Nacc infusion. Glutamate and Trn release were significantly correlated in both groups following intra-Nacc infusion, but in response to intra-Nacc infusions of cocaine only control animals showed a significant correlation between the extracellular levels of Trn and Glu.
Experiment 10: Intravenous Infusions of cocaine
Following initial lesion surgery, all rats in this experiment underwent IV
catheterisation surgery (see General Methods p32). Twelve BLA-lesioned rats and six sham-operated controls were prepared and dialysed in exactly the same manner as described in Expt. 9, except that cocaine infusions were given IV rather than intra-Nacc. The neurochemical response to cocaine was measured following IV
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infusions at doses levels of 0.25 and 0.5 mg cocaine/ infusion. After an hour of baseline sampling (six samples) the first cocaine dose was administered IV (0.25 mg/ infusion/ 4s) followed by the collection of six more samples at 10 min
intervals. The second dose of cocaine (0.5 mg/ infusion/ 4s) was then administered IV and a further six dialysate samples collected. Each sample was handled in exactly the same way as in Expt. 9, being immediately divided for separate DA and amino acid analyses and stored on dry ice until transfer to a storage freezer.
Overall, dialysate samples were collected exactly once every 10 min for 3hr (18
samples/ rat).
Statistical Analyses
Basal extracellular DA and Glu content were analysed initially with a two-way analyses of variance for BLA-lesioned and control animals over the first six 10 min time bins prior to drug treatment: between subject factor Group (2 levels: BLA- lesioned, control), within-subject factor Time (6 levels: 6xl0min time bins). Three-way analyses of variance with repeated measures: with between subject factor of Group (2 levels: BLA-lesioned, control), and within-subject factors Dose (3 levels: baseline, 0.25,0.5mg cocaine/ infusion) and Time (6 levels: 6x10 min time bins, following each infusion) were used to assess the extracellular DA and Glu response to IV infusions of cocaine. Student-Newman-Keuls Post-hoc tests were carried out were applicable.
Results: Exp. 10
Histological assessment confirmed that all probe placements were within the medial core of the Nacc. One lesioned animal was excluded from the final analysis because of incomplete (unilateral) neuronal damage of the BLA and one sham-
operated animal was discounted because of catheter failure. Group numbers in the final statistical analyses were therefore eleven BLA-lesioned and five sham-
operated controls.
IV cocaine infusion: Dopamine efflux
Fig. 20a shows the DA efflux in response to IV administration of cocaine in both BLA-lesioned and sham-operated control animals. A two-way analysis of variance showed that the groups did not differ significantly in their basal DA release. There was no significant effect of Group [F(l,14)=0.57, p=NS] or Time [F(5,70)=0.81, p=NS] and no Group x Time interaction. In response to cocaine, a three-way analysis of variance showed significant main effects of Dose [F(2,28)=17.30, p<0.001] and Time [F(5,70)=l 1.77, p<0.001] and a significant Dose x Time interaction [F(10,140)=4.22 p<0.001]. There was no significant main effect of Group [F(l,14)=1.88, p=NS] and Group x Dose, Group x Time and Group x Dose
X Time interactions were all non-significant. Both BLA-lesioned and control
groups showed a dose- and time-dependent increase in extracellular Nacc DA- efflux following IV infusions of cocaine.