Bell R L, Rodd Z A, Hsu C C, Lumeng L, Murphy J M, McBride W J
Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA.
Pharmacol Biochem Behav. 2003 Apr;75(1):163-71. doi: 10.1016/s0091-3057(03)00069-8.
Selective breeding has been used to develop the alcohol-preferring (P) and -nonpreferring (NP) rats, with the P rat having lower CNS levels of dopamine (DA) and reduced DA innervation in the nucleus accumbens compared with the NP rat. The acoustic startle response (ASR) and prepulse inhibition (PPI) of the ASR are experimental behaviors altered by DA agonists. We examined whether functional differences in amphetamine (AMPH)-modified ASR and PPI exist between P and NP rats. AMPH [0.0 (saline), 1.0, 2.0, or 4.0 mg/kg] was injected 15 min prior to placement into a startle apparatus. After a 5-min habituation period, rats were given approximately twelve 95-, 105-, or 115-dB white-noise burst (ASR) and PPI trials. As adults, P rats were sensitive to AMPH potentiation of the ASR to a greater extent than NP rats. During adolescence, P and NP rats had similar levels of AMPH-potentiated ASR. As adults, NP rats displayed potentiated, rather than disrupted, PPI at the 1.0-mg/kg dose, whereas P rats displayed the expected disrupted PPI at the 4.0-mg/kg dose. As adolescents, NP rats did not display significant differences in PPI after AMPH, whereas P rats displayed dose-dependent disruption of PPI, which was significant at the 4.0-mg/kg dose. The limited effect of AMPH on increasing the ASR and the presence of AMPH-potentiated PPI at the lowest dose in the adult NP rat suggests reduced functioning of the interactions between DA circuits and the neurocircuitry mediating the ASR and PPI, compared with P rats. However, the neurocircuitry mediating PPI does not appear to be fully developed in the adolescent NP rat. The present findings also indicate that lower levels of DA content and immunoreactive fibers in the P rat may not reflect reduced DA neuronal activity, because the P rat displayed AMPH-potentiated ASR, and, at the highest dose, AMPH disruption of PPI during both adulthood and adolescence.
选择性育种已被用于培育嗜酒（P）和不嗜酒（NP）大鼠，与NP大鼠相比，P大鼠中枢神经系统中的多巴胺（DA）水平较低，伏隔核中的DA神经支配减少。听觉惊吓反应（ASR）和ASR的前脉冲抑制（PPI）是受DA激动剂改变的实验行为。我们研究了P大鼠和NP大鼠在苯丙胺（AMPH）修饰的ASR和PPI方面是否存在功能差异。在将大鼠放入惊吓装置前15分钟注射AMPH[0.0（生理盐水）、1.0、2.0或4.0mg/kg]。经过5分钟的适应期后，给大鼠进行大约十二次95、105或115分贝的白噪声猝发（ASR）和PPI试验。成年后，P大鼠比NP大鼠对AMPH增强ASR的作用更敏感。在青春期，P大鼠和NP大鼠的AMPH增强ASR水平相似。成年后，NP大鼠在1.0mg/kg剂量时表现出PPI增强而非破坏，而P大鼠在4.0mg/kg剂量时表现出预期的PPI破坏。在青春期，NP大鼠在注射AMPH后PPI没有显著差异，而P大鼠表现出剂量依赖性的PPI破坏，在4.0mg/kg剂量时具有显著性。AMPH对增加ASR的作用有限，以及成年NP大鼠在最低剂量时存在AMPH增强的PPI，这表明与P大鼠相比，DA回路与介导ASR和PPI的神经回路之间的相互作用功能降低。然而，介导PPI的神经回路在青春期NP大鼠中似乎尚未完全发育。目前的研究结果还表明，P大鼠中较低的DA含量和免疫反应性纤维水平可能并不反映DA神经元活性降低，因为P大鼠在成年期和青春期都表现出AMPH增强的ASR，以及在最高剂量时AMPH对PPI的破坏。
