J.-J. Vanderhaeghen

Opposite Effects of Cholecystokinin Octapeptide (cck-8) and Tetrapeptide (cck-4) After Injection Into the Caudal Part of the Nucleus-accumbens Or Into its Rostral Part and the Cerebral-ventricles

Neurons with colocalized cholecystokinin and dopamine are present predominantly in the ventral tegmental area and project mainly to the caudal part of the medial nucleus accumbens. The activity of this dopamine system can be evaluated by means of the intracranial self-stimulation behavior on male Wistar rats having chronic electrodes implanted into the medial forebrain bundle in the postero-lateral area of the hypothalamus. The direct injection of 150 pmol CCK-8 into the medio-caudal accumbens induced an increase of intracranial self stimulation while a similar administration into its rostral portion produced a slight decrease of intracranial self-stimulation. The administration of 300 pmol CCK-4 into the same medio-caudal part of the accumbens produced an inhibitory action on intracranial self stimulation lasting for 25 min. The injection of 70 to 1300 pmol CCK-4 into the cerebral ventricles produced no change on intracranial self-stimulation. The intracerebroventricular injection of 70 pmol CCK-8 induced a large decrease of intracranial self-stimulation lasting for 20 min. Sodium chloride 0.15 M or unsulphated CCK-8 injection were without effect in either case. These results support the ideas that intracerebroventricular CCK-8 injection inhibits accumbens dopaminergic activity but that CCK-8 injection into the medio-caudal part of the accumbens, where nerve terminals with colocalized CCK and DA are present, facilitates this dopaminergic activity. In addition at the level of medio-caudal accumbens, CCK-8 and CCK-4 have opposite effects.

Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: Blockade by N- methyl-D-aspartate antagonist

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.

Cholecystokinin Neuron Systems and Their Interactions with the Presynaptic Features of the Dopamine Neuron Systems

A unique role for CCK-58 compared to that for CCK-8 has been demonstrated in the modulation of central catecholaminergic mechanisms and neuroendocrine functions. It is of paramount importance to localize CCK-58 immunoreactivity within the brain in order to establish if separate CCK-58- and CCK-8-immunoreactive neuron systems exist. The two most significant actions of CCK-58 are a marked lowering of TSH secretion and a selective increase of DA turnover in DA-CCK co-existing synapses in the nucleus accumbens and tuberculum olfactorium.

Demonstration of a neuropeptide Y (NPY)-like immunoreactivity in the pigeon retina

The distribution of neuropeptide Y (NPY)-like immunoreactivity in the pigeon retina was investigated by fluorescence immunohistochemistry. NPY-positive cells were found in central and peripheral retina. NPY somata were located in the proximal portion of the inner nuclear layer and their processes directed to the inner plexiform layer where they ramified in 3 immunoreactive bands. NPY might play a role as a neurotransmitter or neuromodulator in the pigeon retina.

Co‐existence of Cholecystokinin‐ or Gastrin‐like Peptides with Other Peptides in the Hypophysis and the Hypothalamus

The presence of cholecystokinin and gastrin has been reported in the hypothalamohypophyseal system. These peptides present a peculiar distribution in the hypothalamic nuclei, the median eminence, and the neurohypophysis. CCK and gastrin have close relationships with other peptides like oxytocin, CRF, vasopressin, and the enkephalins; these relationships vary in different projecting areas and in different types of hypothalamic neurons. The functional role of G-CCK in neurosecretion seems to be linked to the role of these closely associated peptides and certainly deserves further investigation.

Distribution of neuropeptide Y immunoreactivity in human visual cortex and underlying white matter

Immunocytochemical techniques have been used to study neuropeptide Y (NPY) distribution in the human visual cortex (Brodmans areas 17, 18 and 19) NPY cell bodies belong mostly to inhibitory (multipolar and bitufted) but also to excitatory (bipolar and some pyramidal) neuronal types. Their distribution is similar in the three cortical areas studied: 20 to 40% of the NPY perikarya are located in the cortical gray matter, mostly in the deep layers, while the remaining 60 to 80% are located in the underlying white matter. Immunoreactive NPY processes form a rich network of intersecting fibers throughout the entire visual cortex. A superficial plexus (layers I and II) and a deep plexus (deep layer V and layer VI) of NPY fibers are present in areas 17, 18 and 19. In area 17, an additional well developed plexus is present in layers IVb and IVc. These plexuses receive branches from long parallel fibers arising from deep cortical layers or underlying white matter and terminating in superficial layers. Local or extrinsic NPY terminals wind around vessels in the cortex as well as in the white matter, and either penetrate them or form clusters of club endings on their walls. Our results suggest a role for NPY in human visual circuitry and in cortical blood flow regulation.

Changes in neurohypophysial cholecystokinin content during oestrous cycle in the rat

Cholecystokinin content in the neurointermediate lobe of the rat pituitary was measured by radioimmunoassay during the different stages of the oestrous cycle. Higher levels were observed in pro-oestrus and oestrus than in metoestrus and dioestrus rats. This difference is similar to the variation observed in the same circumstance concerning oxytocin in the neurohypophysis and neurosecretory activity in magnocellular neurons. These results are discussed in relation to the coexistence of oxytocin and cholecystokinin in neurons of the hypothalamoneurohypophysial system.

NMDA receptor antagonist MK-801 down-regulates rat striatal proenkephalin and protachykinin mRNAs

Using quantitative in situ hybridization, a significant decrease in expression of proenkephalin (27.1%) and of protachykinin mRNAs (20.0%) is observed in the rat caudate-putamen 14 days after daily intraperitoneal administration of N-methyl-D-aspartate receptor antagonist MK-801, 2 mg/kg.

Similar effect of caerulein on intracranial self-stimulation in vagotomized and non-vagotomized rats.

Electrical stimulation eliciting self-stimulation behavior from postero-lateral hypothalamic implanted electrode was controlled by factors that control normal feeding. In this idea, lateral hypothalamic stimulation possessed an appetite whetting property and this is experienced as rewarding. The octapeptide cholecystokinin, a gut hormone, has been experimented upon to produce the complete behavioral sequence of satiety in rats. We observed that an i.p. injection of caerulein (an analog of cholecystokinin) did decrease, in a dose-related manner, the rate for brain self-stimulation. However, a similar effect on the rate of ICSS was measured after a bilateral cut of the vagus nerve at a subdiaphragmatic level. This result suggests that the decreasing effect on ICSS after an i.p. injection of caerulein is not strictly related to feeding. We interpret the decrease of reinforcement induced by caerulein as the action of a general satiety for any object presenting a rewarding value for behavior.

Ontogeny of cholecystokinin receptors in the human striatum.

The distribution of cholecystokinin binding sites was studied by receptor autoradiography in the human striatum at midgestation, birth and adulthood. In the adult, cholecystokinin receptors are inhomogeneously distributed with patches of reduced labeling. In the caudate nucleus but not in the putamen these patches match the striosomal organization as revealed by acetylcholinesterase staining. At midgestation, patches of high density of cholecystokinin receptors are in register with the dopamine D1 receptor-enriched striosomes. At birth, this striosomal organization has already evolved into the adult pattern of higher matrix level in contrast to the striosomal pattern of acetylcholinesterase staining.