New central projections of neuropeptide FF: colateral branching pathways in the brainstem and hypothalamus in the rat.

Neuropeptide FF (NPFF), a morphine modulatory peptide, has been identified within discrete autonomic regions in the brainstem and hypothalamus. Triple fluorescence labelling was employed to identify collateral branching projections of NPFF neurons located within the nucleus tractus solitarius (NTS) and in the region of the hypothalamus between the dorsomedial and ventromedial hypothalamus. Injections of two retrograde tracers, rhodamine- and fluorescein-labelled latex microspheres into the pontine parabrachial nucleus (PBN) and the ventrolateral medulla resulted in labelling of NPFF neurons in the NTS that contained one (double-labelled) or both (triple-labelled) tracers. Within the NTS, most double- and triple-labelled NPFF neurons were localized at the level of the area postrema or just rostral to it and within the medial and dorsomedial subdivisions of the nucleus. Injections of tracers into the PBN and hypothalamic paraventricular nucleus revealed double- and triple-labelled NPFF neurons, a majority of which were located in a zone between the dorsomedial and ventromedial hypothalamus. These results indicate that NPFF neurons in the brainstem and hypothalamus may simultaneously transmit signals to their target nuclei in the brainstem and forebrain. This coordinated signalling may lead to synchronized responses of NPFF target sites and provide insights into the role of this peptide in cardiovascular and nociceptive responses.

Neonatal exposure to the glutamate receptor antagonist MK-801: effects on locomotor activity and pre-pulse inhibition before and after sexual maturity in rats.

Neonatal lesions of the ventral hippocampus in rats lead to post- but not pre-pubertal behavioral changes suggesting adolescent onset of dopaminergic hypersensitivity and providing an animal model of schizophrenia. Neonatal exposure to glutamate receptor antagonists produces accelerated apoptosis leading to neuronal loss in central nervous system structures including the hippocampus. This suggested that neonatal MK-801 might lead to behavioural changes like those reported following ventral hippocampal lesions. Thus, rats received MK-801 (0, 0.5, 1.0 mg/kg ip) on postnatal day 3 (P3) and were tested pre- (P35) and post-pubertally (P56). MK-801 produced an increase in TUNEL staining in the hippocampus and other forebrain structures, confirming the induction of apoptosis. Results showed little difference in locomotor activity between neonatal saline- and MK-801-treated groups during habituation or following saline injection but increased activity was seen in the 0.5 mg/kg MK-801 group following amphetamine (1.5 mg/kg i.p.) at P35 but not P56. In tests of pre-pulse inhibition (PPI), neonatal saline and MK-801 groups showed stable startle amplitudes, minimal responding to the pre-pulse stimuli alone, an increase in PPI with increases in pre-pulse intensity, and reduced PPI with apomorphine (0.1 mg/kg s.c.). At P56, neonatal MK-801 groups tested following vehicle showed less sensitivity to changes in pre-pulse intensity. It was concluded that neonatal MK-801 increases apoptotic cell loss in the hippocampus but does not produce behavioural effects like those seen after neonatal ventral hippocampal lesions. However, neonatal MK-801 did lead to increases in locomotor activity in juveniles but not adults and reduced sensitivity to pre-pulse intensity in PPI tests in adulthood.