Intranigral microinjection of neurotensin suppresses feeding in food deprived rats.

This study was conducted to determine whether the substantia nigra is involved in the anorectic effect of centrally administered neurotensin. Microinjection of neurotensin (2.5 - 10.0 micrograms) into the substantia nigra produced a significant suppression of feeding in 18 hour food deprived rats. To determine if the anorectic effect resulted from a general impairment of sensory-motor functioning, eight behaviors were measured in a separate study. Significant effects were found in only two of the eight behavioral categories (sniffing and eating), and only at the highest neurotensin dose (10.0 micrograms). These results suggest that the substantia nigra may be involved in the anorectic effect of neurotensin.

Evidence that physical dependence on morphine is mediated by the ventral midbrain.

Rats were given daily injections of increasing doses of morphine sulfate (40-100 mg/kg, s.c.), for 4 days. Twenty hours after the last injection of morphine, the animals received bilateral injections of naloxone (1-10 micrograms) into the substantia nigra, ventral tegmental area or sites 2 mm rostral, caudal or dorsal to the site in the nigra. Withdrawal signs were monitored for 20 min after the intracerebral injection. Naloxone administered into the nigra in morphine-dependent rats produced dose-dependent significant increases in wet dog shakes, irritability to touch, teeth chattering, diarrhea and locomotion, compared to morphine-dependent animals that received injections of saline into the nigra. The injection of naloxone (3 micrograms) into the ventral tegmental area of morphine-dependent animals, produced irritability to touch and diarrhea, compared to morphine-dependent controls that received saline in this region of the brain. Significant differences in withdrawal signs were observed between morphine-dependent animals, that received injections of naloxone (3 micrograms) into the nigra and those that received naloxone (3 micrograms) into the ventral tegmental area or rostral or caudal sites. No differences between the substantia nigra and the dorsal sites were observed. However, withdrawal symptoms were produced by injections of naloxone into the substantia nigra and ventral tegmental area, even when the guide cannulae were angled to avoid penetration of sites dorsal to these regions of the brain. Naloxone, injected into the ventral midbrain of non-dependent animals, produced no signs of withdrawal. These studies suggest that the ventral midbrain mediates physical dependence on morphine.

Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia.

Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.

Evidence that the substantia nigra is a component of the endogenous pain suppression system in the rat.

The present study sought to determine whether opiate receptors in the substantia nigra may mediate antinociception produced by systemic morphine. Bilateral intranigral microinjection of naloxone-HCl (0.3-10 micrograms) suppressed the antinociceptive effects of systemically administered morphine sulfate (5 mg/kg, s.c.) on the tail-flick and hot-plate tests in a dose-related manner. Injection of naloxone (3 micrograms) into the ventral tegmental area did not alter antinociception produced by systemic morphine (5 mg/kg, s.c.). These findings support the argument that the substantia nigra is an essential, and previously unrecognized, component of the endogenous pain suppression system.

Bilateral intranigral microinjection of morphine and opioid peptides produces antinociception in rats.

Bilateral intranigral microinjection of morphine produced dose-related and naloxone-reversible antinociceptive effects on the tail-flick and hot-plate tests. Intranigral injection of enkephalin had antinociceptive effects on both tests, and dynorphin had an antinociceptive effect on the hot-plate test. This is the first report of evidence that nigral opiate receptors may mediate antinociception.