Article Figures & Data
Figures
- Figure 1.
Regional differences in nicotine self-administration. A, Self-administration rates (mean infusions per minute with SEM) are depicted as a function of region and session (concentration). A significant interaction between region and treatment (F(7,77) = 3.08; p < 0.01) was found for the first four sessions. #p < 0.05, significantly different compared with respective vehicle trials. A two-way ANOVA with region and high concentration set (12.5, 25, and 50 or sessions 5–7) found that a significant region-by-concentration interaction (F(14,154) = 2.90; p < 0.001). &&p < 0.05, significantly different compared with anterior VTA, medial mammillary nucleus, region dorsal to posterior VTA–lateral to central linear nucleus (CL), and substantia nigra groups. Similarly, a two-way ANOVA with region and low concentration set (0.1, 0.3, 1, 3, and 10 or sessions 9–13) found a significant region-by-concentration interaction (F(28,308) = 2.63; p < 0.0001). **p < 0.05, significantly different compared with anterior VTA, medial mammillary nucleus, region dorsal to posterior VTA–lateral to central linear nucleus, and substantia nigra groups. *p < 0.05, significantly different compared with the medial mammillary nucleus and substantia nigra. B, Effectiveness of each injection site is depicted on coronal drawings [adapted and modified from the atlas by Paxinos and Watson (1997)]. The location of each injection cannula tip is shown in a distinct color, which indicates one of four levels of mean self-administration rates during sessions 5–7. The numbers in the drawings indicate distances from bregma. aVTA, Anterior VTA; CL, central linear nucleus raphé; IP, interpeduncular nucleus; MM, medial mammillary nucleus; PH, posterior hypothalamicnucleus; PN, paranigralnucleus; pVTA, posterior VTA; SN, substantia nigra; SUM, supramammillary nucleus. C, Photomicrograms show the tips of injection cannulas (red arrows) placed for the supramammillary nucleus, posterior VTA, and central linear nucleus.
- Figure 2.
Two-lever discrimination. Data are means plus SEM. Rats received vehicle in session 1 and 25 mm nicotine in sessions 2–5. ANOVAs with two levers over five sessions found that significant lever-by-session interactions for the VTA (n = 13; F(4,48) = 5.29; p < 0.01), central linear nucleus (n = 13; F(4,48) = 2.76; p < 0.05), and supramammillary nucleus (n = 9; F(4,32) = 2.99; p < 0.05). Dunnett's post hoc tests found that active lever presses in session 2–5 were significantly greater than control lever presses in session 1 (*p < 0.05), which did not differ from active lever presses in session 1 or control lever presses in sessions 2–5.
- Figure 3.
Effects of cholinergic antagonists on nicotine self-administration. Data are means plus SEM. Rats (n = 7) self-administered nicotine, nicotine plus mecamylamine, nicotine plus scopolamine, and vehicle over four sessions into the posterior VTA. A repeated ANOVA found that a significant treatment effect (F(3,18) = 8.20; p < 0.01). Similarly, two groups of rats self-administered nicotine, nicotine plus mecamylamine, or vehicle over three sessions into either the central linear nucleus (n = 7) or supramammillary nucleus (n = 8). Repeated ANOVAs found significant treatment effects in the central linear nucleus (F(2,12) = 5.81; p < 0.05) and supramammillary nucleus (F(2,14) = 8.43; p < 0.01). *p < 0.05, significant difference compared with nicotine alone. n., Nucleus; VEH, vehicle.
- Figure 4.
Role of dopamine in nicotine self-administration into the ventromedial midbrain. Rats self-administered 25 or 0.3 mm nicotine after treated with the D1 antagonist SCH 23390 (SCH) (0.05 mg/kg, i.p.) or saline (1 ml/kg). A, Mean infusion rates with SEM (n = 7) are shown. The SCH 23390 treatment significantly reduced the rate of self-infusion of the high nicotine concentration into the posterior VTA (*p < 0.001, after a significant interaction between concentration and treatment; F(1,6) = 17.42; p < 0.01). In addition, the treatment did not enhance nicotine self-administration but tended to reduce self-administration rates of the low nicotine concentration (p = 0.058). B, Mean infusion intervals with SEM as a function of treatment are shown. The first three infusion intervals did not differ under three treatment conditions: nicotine infusion (NIC) with the D1 antagonist pretreatment, nicotine infusion with saline pretreatment, or vehicle infusion (VEH) with saline pretreatment, whereas the last three intervals differed significantly among the treatments (a significant interaction between treatment and first–last interval; F(2,12) = 14.08; p < 0.001). When rats received nicotine with SCH 23390 treatment or vehicle with saline treatment, they self-administered infusions at significantly longer intervals than when they received nicotine with saline treatment during the last three intervals(p<0.01).C, Event records of a representative rat are shown. Each vertical line on the horizontal line indicates the time of an infusion. The number just right of the horizontal line indicates total infusions per session. VEH, Vehicle; SCH, SCH 23390. D, Coadministration of the D2 receptor agonist quinpirole into the posterior VTA (n = 13) or central linear nucleus (n.) (n = 6), which inactivates local dopamine neurons, reduced nicotine self-administration. Repeated ANOVAs with nicotine, nicotine plus quinpirole, and vehicle found significant main effects for the VTA (F(2,24) = 8.79; p < 0.05) and central linear nucleus (F(2,10) = 4.59; p < 0.05). *p < 0.05, significant difference compared with nicotine alone.
