Frye G D, Baumeister A A, Crotty K, Newman K D, Kotrla K J
Neuropharmacology. 1986 Jul;25(7):717-26. doi: 10.1016/0028-3908(86)90087-0.
In rats, bilateral injection of muscimol (30-60 ng/site) into the medial substantia nigra zona reticulata exerted an antinociceptive effect in the hotplate and tail-flick tests. Injections of muscimol into the substantia nigra also induced intense stereotyped behavior and self-injurious behavior (SIB). Tail-flick and hindpaw-lick responses were inhibited between 30 and 120 min after muscimol, but recovered by 240 min. The antinociceptive responses were not due to motor impairment or ataxia induced by muscimol because a variety of highly-coordinated stereotyped behavioral responses, including rearing, sniffing, head bobbing and licking occurred concurrently. Injection of muscimol into the deep mesencephalic nucleus (DpMcN) also inhibited the tail-flick and hindpaw-lick responses and caused stereotyped behavior but did not induce self-injurious behavior. Injections of muscimol into the substantia nigra, angled (45 degrees) to avoid passing through the deep mesencephalic nucleus, still exerted antinociceptive activity and caused self-injurious behavior. Bilateral microinjections of baclofen (300 ng), 4,5,6,7-tetrahydroisoxazols (5,40c)pyridin-3-ol (THIP; 300 ng), sodium valproate + D,L-diaminobutyric acid (1 microgram), substance P (2.5 micrograms) or D-Pro2-D-Trp7.9-substance P (2.5 micrograms), all suppressed hindpaw-lick responses, although only THIP reduced tail-flick responses. None of these treatments evoked self-injurious behavior. Naloxone (10 mg/kg), picrotoxin (5 mg/kg) or atropine (10 mg/kg) injection of muscimol into the substantia nigra (60 ng) or a single pretreatment with p-chlorophenylalanine diethyl ester (PCPA; 500 mg/kg; 48 hr prior to muscimol) failed to suppress the hindpaw-lick response or self-injurious behavior. These results suggest that the injection of muscimol into the substantia nigra evokes a centrally-mediated antinociception which alone is not sufficient to induce self-injurious behavior. Both antinociception and self-injurious behavior after injection of muscimol into the substantia nigra appear unrelated to cholinergic, serotoninergic, or naloxone-sensitive nociceptive systems; however, the role of activation of gamma-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.
在大鼠中，向黑质网状带内侧双侧注射蝇蕈醇（30 - 60纳克/部位）在热板和甩尾试验中产生了镇痛作用。向黑质注射蝇蕈醇还会诱发强烈的刻板行为和自我伤害行为（SIB）。在注射蝇蕈醇后30至120分钟内，甩尾和后爪舔舐反应受到抑制，但在240分钟时恢复。这种镇痛反应并非由蝇蕈醇引起的运动障碍或共济失调所致，因为同时出现了多种高度协调的刻板行为反应，包括直立、嗅探、点头和舔舐。向中脑深部核（DpMcN）注射蝇蕈醇也会抑制甩尾和后爪舔舐反应，并引起刻板行为，但不会诱发自我伤害行为。向黑质注射蝇蕈醇时，呈一定角度（45度）以避免穿过中脑深部核，仍能发挥镇痛活性并导致自我伤害行为。双侧微量注射巴氯芬（300纳克）、4,5,6,7 - 四氢异恶唑并[5,4 - c]吡啶 - 3 - 醇（THIP；300纳克）、丙戊酸钠 + D,L - 二氨基丁酸（1微克）、P物质（2.5微克）或D - Pro2 - D - Trp7,9 - P物质（2.5微克），均能抑制后爪舔舐反应，不过只有THIP能降低甩尾反应。这些处理均未诱发自我伤害行为。向黑质（60纳克）注射蝇蕈醇后注射纳洛酮（10毫克/千克）、印防己毒素（5毫克/千克）或阿托品（10毫克/千克），或者在注射蝇蕈醇前用对氯苯丙氨酸二乙酯（PCPA；500毫克/千克；提前48小时）进行单次预处理，均未能抑制后爪舔舐反应或自我伤害行为。这些结果表明，向黑质注射蝇蕈醇会引发中枢介导的镇痛作用，而这种镇痛作用本身不足以诱发自我伤害行为。向黑质注射蝇蕈醇后的镇痛作用和自我伤害行为似乎与胆碱能、血清素能或纳洛酮敏感的伤害感受系统无关；然而，γ - 氨基丁酸（GABA）受体激活在蝇蕈醇这些作用中的作用仍有待阐明。
