Figure 6.
pHSVsiLA1 delivery into the VP inhibits alcohol intake in HAD rats. (A–C) HAD rats were microinfused with pHSVsiLA1 (n = 6) or PBS (control; n = 6) into the VP and examined for intake of alcohol (10% v/v) (A), water (B), or sucrose (C) in a home-cage bottle paradigm for 90 min. Alcohol results are expressed in grams per kilogram (g/kg). Prior to surgery, BACs in the PBS control and pHSVsiLA1 groups were 112 mg%/dL ± 13 and 118 mg%/dL ± 25, respectively. Two-way ANOVA revealed significant main effects of Day [F(28,140) = 5.58, P < 0.001], Group [F(1,5) = 86.184, P < 0.001], and a significant interaction for Day × Group [F(28,140) = 5.35, P < 0.001]. Relative to the control group, significant reductions in alcohol drinking were observed in the pHSVsiLA1-treated group from days 3–25 (Tukey post hoc test). Alcohol intake was similar during days 26–30 for the pHSVsiLA1 and PBS control groups. (B) Water intake (mL/kg)/22.5 h was also similar across pre-surgical days and post-surgical days 1–10 between the pHSVsiLA1 and PBS control groups. (C) Sucrose intake in the two-bottle choice home-cage paradigm over the 90-min period. ANOVA revealed a significant session effect [F(7,74) = 3.616, P < 0.0001]. Specifically, both the control and pHSVsiLA1 pre-surgery groups demonstrated significantly higher drinking than the post-surgery groups on day 3 (P < 0.01). However, no differences were observed between the two groups at pre-surgery or at any post-surgery time point (P > 0.01). (D) HAD rats were given the scrambled amplicon pHSVsiNC (n = 6) or PBS (control; n = 6) into the VP and examined for alcohol consumption. Results are expressed in grams per kilogram (g/kg) during the daily 90 min alcohol sessions. Prior to surgery, BACs in the PBS and pHSVsiNC groups were 133 mg%/dL ± 26 and 122 mg%/dL ± 21, respectively. ANOVA revealed a significant session effect [F(7, 80) = 11.96, P < 0.0001], but no group effects. Specifically, drinking in the both the control and pHSVsiNC pre-surgery groups was significantly greater than in the post-surgery groups on days 3 and 4 (P < 0.01). However, no differences were observed between the two groups at pre-surgery or at any post-surgery time point (P > 0.01). Significant effects were identified using the Newman–Keuls post hoc test.