Neurochemical changes in the substantiae nigrae and caudate nuclei following acute unilateral intranigral infusions of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Acute unilateral intranigral infusions of MPTP at doses (200 micrograms) which produce robust contralateral rotation in the rat induced significant neurochemical changes in the ipsilateral as well as contralateral nigrostriatal systems. There were pronounced increases in the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the ipsilateral substantia nigra and a significant decrease in the levels of DA in the ipsilateral caudate nucleus while opposite changes occurred in the contralateral substantia nigra and caudate nucleus. The DOPAC:DA and HVA:DA ratios were significantly higher in the ipsilateral caudate nucleus indicating increased activity of the ipsilateral nigrostriatal DA neurones. The levels of noradrenaline and 4-hydroxy-3-methoxyphenylethyline glycol (MHPG) increased and decreased significantly in the ipsilateral and contralateral substantia nigra, respectively, but there were no significant changes in the caudate nuclei. The levels of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly in the ipsilateral substantia nigra and caudate nucleus as well as in the contralateral caudate nucleus but did not increase significantly in the contralateral substantia nigra. The 5-HIAA:5-HT ratio was significantly decreased in the contralateral caudate nucleus indicating a reduced activity of the contralateral nigrostriatal 5-HT neurones. The data thus indicate that MPTP applied to one substantia nigra is capable of producing profound neurochemical changes not only locally but also in the ipsilateral striatum as well as in the contralateral nigrostriatal system. Previous neuropharmacological studies have suggested that the rotation induced by intranigral MPTP may be mediated via dopamine released from dendrites in the pars reticulata in response to MPTP.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of mating behaviour in the female rat by gonadotropin-releasing hormone in the ventral tegmental area: effects of selective destruction of the A10 dopamine neurones.

Microinfusions of gonadotropin-releasing hormone (GnRH) into the ventral tegmental area (VTA) potentiated lordosis behaviour in oestrogen-primed ovariectomised female rats. Facilitation was observed within 5 min after the infusion and lasted for about 90 min. When GnRH was infused into the VTA of oestrogen-primed animals which were previously subjected to 6-hydroxydopamine treatment (to destroy the A10 dopamine cells), it produced a marked facilitation of lordosis lasting for about 24 h. These results suggest that the A10 dopamine neurones in the VTA may be critically involved in the mechanisms by which GnRH may modulate midbrain circuits involved in the regulation of lordosis behaviour in the female rat. The lesion studies also imply that the A10 dopamine neurones function as inhibitory neurones regulating lordosis behaviour by suppressing the activity of those cells in the VTA which are sensitive to GnRH. Removal of this inhibitory input leads to an exaggerated response.

The effect of immunization against somatostatin on growth rates and growth hormone secretion in the chicken.

The effect of both active passive immunization against somatostatin on growth rate and growth hormone levels was studied in chickens. Passive immunization against somatostatin by administration of antiserum had no effect on rate of growth of chickens and no persistent effect on circulating growth hormone (GH) levels. In acute experiments, administration of anti-somatostatin serum caused a marked elevation of GH levels in chickens at both 4 and 8 weeks of age, but the relative stimulation was greater in the older birds. Active immunization against somatostatin significantly stimulated growth rate in chickens, but was not shown to have a clear effect on circulating GH levels. These data suggest that somatostatin control over GH secretion may not be fully developed in the chicken at 4 weeks of age, but that immuno-neutralization of somatostatin can produce an increase rate of growth in chickens similar to that seen in mammals.

Endogenous opioid peptides participate in the modulation of prolactin release in response to cervicovaginal stimulation in the female rat.

Naloxone, a specific opiate receptor antagonist, was used to evaluate the influence of endogenous opiate peptides on PRL secretion during various stages of the estrous cycle and after cervicovaginal stimulation. Naloxone (0.2 mg/kg, iv) administered at 0930 h suppressed basal 1000 h PRL levels on each day of the estrous cycle, but had no effect on the PRL surges occurring on the afternoon of proestrus and estrus. These afternoon surges could only be suppressed when naloxone was given immediately before the onset of the surge at 1330 h, suggesting a critical period for naloxone action. Later injections (at 1530 and 1730 h) had no further suppressive effects, although these injections suppressed the basal PRL secretion occurring during diestrous days I and II to near undetectable levels. In contrast, the immediate (1000 h) and afternoon PRL discharges triggered by cervicovaginal stimulation at 0930 h on proestrus, estrus, and diestrous day I were significantly suppressed by a single injection of naloxone, but only when it was administered before application of the stimulus. Moreover, this single naloxone injection significantly inhibited the long term PRL surges occurring during days 2 and 4 of pseudopregnancy in animals stimulated on estrus and diestrous day I. Naloxone treatment significantly shortened the duration of pseudopregnancy but did not prevent it, indicating that only minimal levels of PRL may be necessary to initiate and maintain pseudopregnancy. This striking difference in the time at which naloxone suppressed the stimulus-induced PRL discharges (compared to the spontaneous surges) suggests that endogenous opiate peptides also process the sensory information necessary for establishment of PRL surges during pseudopregnancy. The marked dependence of the spontaneous as well as the stimulus-induced PRL discharges on the stage of the estrous cycle support established evidence that ovarian steroids enhance endogenous opiate activity or facilitate the transfer of information along opiatergic pathways for the generation of PRL surges.

Studies on the sympathetic nervous system: the Valsalva like manoeuvre in sheep.

The Valsalva like manoeuvre (VLM) was examined as a test of the responsiveness of the autonomic nervous system in sheep. Within individuals, imipramine pretreatment enhanced the peak blood pressure and heart rate responses to the VLM and atropine prolonged the tachycardia without influencing the peak responses. Between individuals, the peak blood pressure response was related to the degree of hypotension during raised airway pressure (r = 0.77). The degree of hypotension was, in turn, related to gut fill (r = 0.64). Differences in gut fill were ascribed as a cause of variation in the heart rate and blood pressure responses between individual sheep and between the Scottish Blackface and Southdown breeds.