Hasenöhrl R U, Gerhardt P, Huston J P
Institute of Physiological Psychology, Heinrich-Heine-University Düsseldorf, Federal Republic of Germany.
Exp Neurol. 1992 Feb;115(2):282-91. doi: 10.1016/0014-4886(92)90063-v.
The conditioned corral preference paradigm was used to assess reinforcing effects of substance P (SP) and its N- and C-terminal fragments injected unilaterally into the region of the nucleus basalis magnocellularis (NBM) in rats. Behavioral testing was carried out in a circular open field, consisting of 4 quadrants equally preferred by the animals prior to conditioning. A single conditioning trial was performed. Rats received one microinjection (0.5 microliter) of SP (0.74 pmol), of the N-terminal fragment SP (1-7) and the C-terminal fragment analog DiMe-C7 (each at doses of 0.074, 0.74, and 74 pmol), or vehicle (phosphate-buffered saline; PBS). After injection the rats were placed into the open field with the four quadrants being separated by Plexiglas barriers (closed corral). During the test for conditioned corral preference, when provided a choice between the four quadrants, only those rats injected with SP and the equimolar dose of DiMe-C7 (0.74 pmol) spent more time in the treatment corral, indicative of a positively reinforcing action. None of the other doses of DiMe-C7 and of SP(1-7) influenced the preference behavior. For rats injected with 0.74 pmol SP, SP (1-7), and DiMe-C7, a behavioral analysis was performed for the 15 min conditioning trial. SP and DiMe-C7 reduced rearing and grooming behavior, whereas DiMe-C7 and SP(1-7) increased locomotor activity. However, the acute behavioral effects of SP and its fragments were not correlated with the subsequent place preference behavior during the test trial. The results are discussed in the framework of a structure/activity relationship for the positively reinforcing properties of SP in the region of the NBM. Furthermore, neuropathological implications of the present data are considered, since the homologous nucleus basalis of Meynert in man is known to degenerate in Alzheimer's disease, which is characterized behaviorally by a progressive deterioration in associative functioning.
条件性畜栏偏好范式被用于评估在大鼠中单侧注射到基底大细胞核（NBM）区域的P物质（SP）及其N端和C端片段的强化作用。行为测试在一个圆形开放场中进行，该开放场由4个象限组成，在条件反射前动物对这4个象限的偏好程度相同。进行了一次单一的条件反射试验。大鼠接受一次微量注射（0.5微升）的SP（0.74皮摩尔）、N端片段SP（1-7）和C端片段类似物DiMe-C7（各剂量为0.074、0.74和74皮摩尔）或溶剂（磷酸盐缓冲盐水；PBS）。注射后，将大鼠放入开放场中，四个象限由有机玻璃屏障隔开（封闭畜栏）。在条件性畜栏偏好测试中，当在四个象限之间进行选择时，只有那些注射了SP和等摩尔剂量的DiMe-C7（0.74皮摩尔）的大鼠在处理畜栏中花费了更多时间，这表明有正向强化作用。其他剂量的DiMe-C7和SP（1-7）均未影响偏好行为。对于注射了0.74皮摩尔SP、SP（1-7）和DiMe-C7的大鼠，对15分钟的条件反射试验进行了行为分析。SP和DiMe-C7减少了竖毛和梳理行为，而DiMe-C7和SP（1-7）增加了运动活动。然而，SP及其片段的急性行为效应与测试试验期间随后的位置偏好行为无关。在NBM区域中SP的正向强化特性的结构/活性关系框架内讨论了结果。此外，考虑到本数据的神经病理学意义，因为已知人类中同源的迈内特基底核在阿尔茨海默病中会退化，而阿尔茨海默病在行为上的特征是联想功能逐渐恶化。
