Article Figures & Data
Figures
- Figure 1.
Effect of amphetamine on ATF2, ATF3, and ATF4 mRNA expression in striatum. Time course of acute and repeated (7 d) amphetamine-induced (4 mg/kg, i.p.) ATF2 (a), ATF3 (b), and ATF4 (c) mRNA levels. Data points represent mean ± SEM relative induction of mRNA compared with saline-injected controls (Ctrl) (n = 4). Asterisks denote statistical difference from saline. Effect of acute and repeated amphetamine injections on ATF2 (d, g), ATF3 (e, h), and ATF4 (f, i) mRNA levels at 1 h (d–f) or 3 h (g–i) after the last amphetamine injection.
- Figure 2.
Effect of stress on ATF2, ATF3, and ATF4 mRNA expression in striatum. a–c, Time course of ATF2, ATF3, and ATF4 mRNA levels by acute restraint stress. Points represent mean ± SEM relative induction from nonstressed controls (n = 4). d–f, Effect of acute and repeated restraint stress on ATF2, ATF3, and ATF4 mRNA levels compared with nonstressed controls (Ctrl) at 1 h after the last stress. Asterisks denote statistical difference (*p < 0.05) from nonstressed controls.
- Figure 3.
HSV-mediated ATF3 overexpression in nucleus accumbens. Double fluorescent immunohistochemistry demonstrating coexpression of GFP (a) and ATF3 (b) in rat nucleus accumbens, along with a merged image (c). Coexpression of GFP and ATF3 was >95%. Similar results were obtained for ATF2 and ATF4 (data not shown). d, Representative injection site and expression pattern. ac, Anterior commissure; AcbC, nucleus accumbens core; AcbSh, shell.
- Figure 4.
Effect of viral-mediated overexpression of ATF2, ATF3, or ATF4 in nucleus accumbens on spontaneous and amphetamine-stimulated locomotor activity. Time course of spontaneous locomotor activity for HSV-ATF2 (a), -ATF3 (b), and -ATF4 (c) and saline-induced activity. Bottom panels show amphetamine-stimulated locomotor activity (2 mg/kg, i.p.) 3 d after bilateral intra-NAc injections of HSV-ATF2 (d), -ATF3 (e), or -ATF4 (f) when transgene expression is maximal. Control animals received injections of HSV-GFP. Points represent mean ± SEM beam breaks in 10 min bins (n = 6–8). Rats were allowed 60 min to habituate to the test chamber before amphetamine was injected.
- Figure 5.
Effect of viral-mediated overexpression of ATF2, ATF3, or ATF4 in the nucleus accumbens on anxiety-related behavior. HSV vectors overexpressing GFP (control), ATF2, ATF3, or ATF4 were injected bilaterally in the nucleus accumbens. a–c, Effect of ATF2, ATF3, or ATF4 on time spent in the open arm of the elevated plus maze. Error bars represent mean ± SEM time spent on the open arms during a 5 min session. The ATF2 experiment was conducted under a low-anxiety condition, and the ATF3 and ATF4 experiments were conducted under high-anxiety (brighter light) conditions (n = 4–8). d–f, Total distance moved on the elevated plus maze for rats overexpressing ATF2, ATF3, or ATF4. g–i, Sucrose neophobia subsequent to overexpression of ATF2, ATF3, or ATF4. Error bars represent milliliter of a 1% sucrose solution consumed by naive rats across a 30 min session (n = 4–8). Asterisks denote significant difference from HSV-GFP control.
- Figure 6.
Effect of viral-mediated overexpression of ATF2, ATF3, or ATF4 in the nucleus accumbens on depression-related behavior. HSV vectors overexpressing GFP, ATF2, ATF3, or ATF4 were injected bilaterally in the nucleus accumbens. a–c, Effect of ATF2, ATF3, or ATF4 on latency to immobility in the forced swim test. Error bars represent mean ± SEM seconds latency to immobility (1 s immobility) during a 5 min test session (n = 6–8). d–f, Total immobility time for rats overexpressing ATF2, ATF3, or ATF4 in nucleus accumbens. g–i, Effect of ATF2, ATF3, or ATF4 overexpression on sucrose preference. Data represent mean ± SEM milliliter of water or 1% sucrose solution consumed over 10 min using a two-bottle choice procedure (n = 5–8). Asterisks denote significant difference from HSV-GFP control.
Tables
- Table 1.
Effect of amphetamine on ATF2, ATF3, and ATF4 mRNA expression in the nucleus accumbens
Conditions ATF2 (3 h) ATF3 (1 h) ATF4 (3 h) Acute amph Sal 1.00 ± 0.03 1.00 ± 0.09 1.00 ± 0.09 Amph 0.98 ± 0.05 1.87 ± 0.26* 1.79 ± 0.30* Repeated amph Sal 1.00 ± 0.03 1.00 ± 0.09 1.00 ± 0.09 Amph 1.12 ± 0.03* 1.12 ± 0.12 1.49 ± 0.08* -
Values are mean ± SEM fold induction of mRNA. Asterisks denote statistical difference from saline control group (Sal). amph, Amphetamine group; Acute, single injection; Repeated, 7 daily injections.
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- Table 2.
Effects of CREB/ATF family transcription factors in the nucleus accumbens on emotional behavior
CREB family protein Anxiety-like behavior Depression-like behavior Drug sensitivity CREB ↓ ↑ ↑ ↓ ↓ ATF3 ↓ ↓ ↑ ↓ ↓ ATF4 ↓ ↓ ↑ ↑ ↓ ICER ↑ ↑ ↓ ↓ ↓ ↑ ↑ ATF2 ↑ ↓ ↓ ↑ -
The table summarizes the behavioral effects of overexpression of each protein in the nucleus accumbens based on data, in addition to the present study, reported by Carlezon et al. (1998), Pliakas et al. (2001), Barrot et al. (2002), and Green et al. (2006). The ICER/ATF2 phenotype represents a “CREB antagonist” phenotype, because overexpression of mCREB, a dominant-negative CREB mutant, produces equivalent effects.
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