M. Del Fiacco

Possible stimulatory role of brain dopamine in the copulatory behavior of male rats

Abstract Apomorphine and a combination of Ro 4-4602 with L-DOPA increase the copulatory behavior of male adult rats with a low basal level of sexual activity. This effect is prevented by haloperidol. This drug also suppresses the spontaneous copulatory behavior in rats with high basal level of sexual activity.

Topographical localization of substance P in the human post-mortem brainstem. An immunohistochemical study in the newborn and adult tissue

The localization of substance P-immunoreactive nervous structures in the newborn and adult human brainstem is studied by the indirect immunofluorescence technique of Coons and collaborators. Substance P-containing perikarya, nerve fibres and terminals are widely and unevenly distributed in several areas of the human brainstem, with a location similar to that described in other mammals; however, some remarkable differences are detectable, which speak in favour of the existence of species differences. For example, in the human brain there is a dense plexus of substance P-immunoreactive fibres in the cuneate fasciculus. The use of the newborn tissue is very helpful in the detection of the immunoreactive neuronal cell bodies. The comparative study of the newborn and the adult tissue reveals that the distribution of the substance P-like immunoreactivity changes in man during ontogeny and results in a more complete map of the substance P-containing neuron system.

Effect of discrete kainic acid-induced lesions of corpus caudatus and globus pallidus on glutamic acid decar☐ylase of rat substantia nigra

Locally applied kainic acid was used in order to destroy pallidal perikarya without damaging axons en passage, in an effort to clarify the role of the globus pallidus as a source of nigral GABAergic terminals. Rats were microinjected unilaterally with kainic acid in the globus pallidus, head, body and tail of the caudate and were sacrificed 7 days later. The forebrain of each rat was examined histologically in order to establish the extent of the lesion and nigral glutamate decarboxylase (GAD) was assayed as a marker of GABAergic terminals. Kainic acid produced in the globus pallidus loss of neuronal perikarya and reactive gliosis. Large multipolar neurons of the globus pallidus were characteristically absent on the lesioned-side. Lesions of the pallidum resulted in a non-significant (5.5%) reduction of nigral GAD. Kainate lesions restricted to the head of the caudate resulted in a significant (19%) drop of nigral GAD, while lesions of the caudate body provided the largest reductions of nigral GAD (53%). Lesions of the caudate tail were without effect. The results indicate that nigral GAD arises mostly from the body and, in part, also from the head of the caudate but not from the globus pallidus or from the tail of the caudate.

Calcitonin gene-related peptide in the human trigeminal sensory system at developmental and adult life stages: immunohistochemistry, neuronal morphometry and coexistence with substance P.

The distribution of calcitonin gene-related peptide (CGRP) has been examined by the indirect immunofluorescence technique in the Gasserian ganglion and spinal nucleus of the human trigeminal nerve. In the ganglion CGRP is present in almost 50% of primary sensory neurons, in varicose and non-varicose nerve fibres and in pericellular basket-like plexuses around non-immunoreactive ganglionic perikarya. Morphometric analysis reveals that the CGRP-positive neuronal population is heterogeneous in cell size. Observation of specimens from subjects at fetal, perinatal and adult life stages reveals that the percentage of CGRP-immunoreactive cells reaches a maximum at perinatal stages and then remains constant, declining only in old age. Pericellular basket-like nerve fibres are detectable only in fetal and pre-term and full-term newborn tissue. Coexistence between CGRP and substance P (SP) occurs, SP being present in about one quarter of the CGRP-immunoreactive neurons and CGRP being localized in a little more than half of the SP-immunoreactive neurons. However, perikarya, nerve fibres and pericellular fibres containing only one or other peptide are also present. Bundles of immunoreactive fibres and dot-like nerve terminals occur in the spinal tract and superficial and deep regions of the spinal trigeminal nucleus. A particularly dense plexus is present in the peripheral nuclear layers. Double immunostaining shows a similar regional distribution for SP. However, in inner substantia gelatinosa the density of CGRP-immunoreactive fibres is much higher than that of SP-immunoreactive ones. The results obtained add information to our knowledge of the organization of neurochemically identified neurons in the human trigeminal sensory system.

The human hippocampal formation and parahippocampal gyrus: localization of substance P-like immunoreactivity in newborn and adult post-mortem tissue.

The localization of substance P-like immunoreactive nervous structures in the human post-mortem hippocampal formation and parahippocampal gyrus was studied by the indirect immunofluorescence technique of Coons and Kaplan (1950), J. exp. Med. 91, 1-9. Specimens were obtained from brains of both newborn and adult subjects. Substance P-positive perikarya were easily detectable in these regions, being particularly abundant in the stratum oriens of the hippocampus and in the hilus of the fascia dentata. The nerve fibres and terminals were also widely and unevenly distributed. Comparison of the newborn and adult tissue revealed differences in the distribution of substance P-like immunoreactivity in ontogenetic stages. Our results, together with data available in the literature, further suggest that substance P is differently distributed in the various cortical areas of the human brain, and that the distribution of substance P may vary among species.

Ipsiversive turning behaviour after discrete unilateral lesions of the dorsal mesencephalic reticular formation by kainic acid

Discrete axon-sparing lesions were placed unilaterally in the mesencephalon by the local injection of kainic acid. Unilateral lesions of the dorsal reticular formation just beneath the superior colliculus and lateral to the periacqueductal grey resulted in consistent ipsiversive apomorphine-induced circling. Only weak motor asymmetries were observed after unilateral lesions restricted to the superior colliculus or to the periacqueductal grey. The results indicate that the dorsal mesencephalic reticular formation plays an essential role as an output station for striatal postural functions.

Bortezomib Treatment Produces Nocifensive Behavior and Changes in the Expression of TRPV1, CGRP, and Substance P in the Rat DRG, Spinal Cord, and Sciatic Nerve

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established “chronic” schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

Evidence for the presence of substance P-like immunoreactivity in the human cerebellum ☆

Preliminary results on the localization of substance P-like immunoreactivity in the human cerebellum are presented. Cerebella from newborn and adult subjects were examined. While only sporadic positive fibres were detected in the adult tissue, the immunoreactive material appeared more abundant in the cerebella from newborn subjects. Varicose and non-varicose fibres and dot-like nerve terminals were present with different density in various regions. The paucity of immunoreactive perikarya suggests that most of the cerebellar substance P-like immunoreactive material has an extrinsic origin.

Neuropeptides in the human celiac/superior mesenteric ganglionic complex: An immunohistochemical study

The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine (PHI), calcitonin gene-related peptide (CGRP), substance P (SP), somatostatin (SOM), galanin (GAL) and enkephalins (ENK) is studied in the human celiac/superior mesenteric ganglionic complex of pre- and full-term newborns, and adult subjects by means of immunohistochemistry. The antisera used labelled nerve fibres and terminal-like networks for each examined peptide, as well as VIP- and SOM-positive postganglionic neurons. Differences in the relative amount and density of the structures immunoreactive to the various peptides were observed. Moreover, variations in the amount and type of labelled elements were appreciable for each peptide when specimens from subjects at perinatal and adult ages were compared. Double-labelling immunofluorescence for SP and each other peptide showed that co-localization with SP is very frequent for CGRP, moderate to scarce for GAL and SOM, and rare to absent for PHI, VIP and ENK. VIP-, ENK- and CGRP-immunolabeled perikarya bearing the morphological features of the small intensely fluorescent (SIF) cells occurred in the organ. The presence of a paraganglion in one of the specimens examined allowed the detection of VIP- and ENK-positive cell bodies and VIP-, ENK-, SP- and GAL-like immunoreactive varicose nerve fibres in it. The results obtained provide substantial morphological data in support of the involvement of the examined peptides in the chemical interneuronal signalling in the human celiac/superior mesenteric ganglia.

Lack of copulatory behaviour in male castrated rats after p-chlorophenylalanine.

1 The effect of p‐chlorophenylalanine (PCPA) on the copulatory behaviour of normal and castrated male rats with females in oestrus was studied. 2 Castration 2 months before the experiment completely prevented the increased copulatory behaviour produced by PCPA in normal rats. 3 The administration of testosterone restored the copulatory behaviour in the castrated rats indicating that testosterone is essential for this behaviour.