SUMMARY1. Field stimulation of adrenal nerves was used to study nervous control of adrenal catecholamine secretion in isolated, retrogradely perfused, bovine adrenal glands.2. Secretion of both adrenaline and noradrenaline was maximal at 10 Hz. Secretion at 2 Hz was < 10 % of maximum. Stimulating with trains of pulses at ten times the average frequency for 1 s out of every 10 s gave 2-fold greater secretion at 2 Hz average frequency, similar release at 5 Hz, and only half the secretion at 10 Hz, compared to continuous stimulation at the average frequency.3. At 10 Hz, adrenaline and noradrenaline secretion was virtually abolished by tetrodotoxin (1 /tM), but was only reduced by 75°% by prolonged perfusion with a combination of mecamylamine (5/tM) and atropine (1 ,M). Mecamylamine and atropine completely abolished the secretary response to 2 Hz stimulation. Tetrodotoxin had no significant effect on secretion induced by perfusing glands with nicotine (5 /SM), while mecamylamine abolished this response. Mecamylamine and atropine had no effect on secretion induced by K+ depolarization.4. The secretion of adrenaline and noradrenaline induced by 10 Hz stimulation was not inhibited by naloxone at either 1 or 30 /tM.5. The results suggest that bovine adrenal chromaffin cells, like those in the rat, receive a significant non-cholinergic secretomotor innervation. In contrast to the rat, however, the non-cholinergic component in the bovine adrenal is negligible at lowfrequency nerve stimulation and substantial at higher frequencies, and is not antagonized by naloxone. The identity of the non-cholinergic transmitter remains to be determined.

1. Autoradiographic binding studies have shown that the AT(1) receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT(1) receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord. 2. While there are differences between species, AT(2) receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat. 3. Circulating AngII acts on AT(1) receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking. 4. Centrally administered AngII may act on AT(1) receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion. 5. Recent evidence shows that centrally administered AT(1) antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses. 6. Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT(1) receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

Progressive cell loss is observed in the striatum, cerebral cortex, thalamus, hypothalamus, subthalamic nucleus and hippocampus in Huntington disease. In the striatum, dopamine-responsive medium spiny neurons are preferentially lost. Clinical features include involuntary movements, gait and orofacial impairments in addition to cognitive deficits and psychosis, anxiety and mood disorders. We utilized the Cre-LoxP system to generate mutant mice with selective postnatal ablation of D1 dopamine receptor-expressing striatal neurons to determine which elements of the complex Huntington disease phenotype relate to loss of this neuronal subpopulation. Mutant mice had reduced body weight, locomotor slowing, reduced rearing, ataxia, a short stride length wide-based erratic gait, impairment in orofacial movements and displayed haloperidol-suppressible tic-like movements. The mutation was associated with an anxiolytic profile. Mutant mice had significant striatal-specific atrophy and astrogliosis. D1-expressing cell number was reduced throughout the rostrocaudal extent of the dorsal striatum consistent with partial destruction of the striatonigral pathway. Additional striatal changes included up-regulated D2 and enkephalin mRNA, and an increased density of D2 and preproenkephalin-expressing projection neurons, and striatal neuropeptide Y and cholinergic interneurons. These data suggest that striatal D1-cell-ablation alone may account for the involuntary movements and locomotor, balance and orofacial deficits seen not only in HD but also in HD phenocopy syndromes with striatal atrophy. Therapeutic strategies would therefore need to target striatal D1 cells to ameliorate deficits especially when the clinical presentation is dominated by a bradykinetic/ataxic phenotype with involuntary movements.