Evaluation of the role of antinociception in self-injurious behavior following intranigral injection of muscimol

Abstract

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 120min 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°) 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 (1μg), substance P (2.5 μg) or d-Pro 2 d-Trp 7,9-substance P (2.5 μg), 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 γ-aminobutyric acid (GABA) receptors in these actions of muscimol also remains to be clarified.