Behavioral effects of neurotoxic lesions of the ascending monoamine pathways in the rat brain.

Abstract

Intracranial microinjections of 6-hydroxydopamine or 5,6-dihydroxytryptamine into six ascending monoamine pathways produced the expected patterns of depletion of telencephalic serotonin, dopamine, and norepinephrine. Serotonin level was specifically lowered after dorsal or median raphe lesions but not after mesolimbic or nigrostriatal system lesions which lowered both norepinephrine and dopamine. Lesions in the locus coeruleus or ventral noradrenergic bundle lowered only norepinephrine, and locus coeruleus lesions elevated serotonin level. Behavior was examined in an open field, one-way active avoidance, and two passive avoidance tasks, and measures were taken of water consumption and body weight. Dorsal raphe lesions had no effect on any of the measures; the other five lesion groups exhibited deficient acquisition of the one-way active avoidance task. In the appetitive passive avoidance task, only the substantia nigra lesion group exhibited a deficiency. In the step-through passive avoidance task, both the substantia nigra and the median raphe groups exhibited a deficit, with the median raphe group exhibiting hyperactivity in the start box during testing. Water consumption was decreased by lesions in the ventral noradrenergic bundle during the first postoperative week and was increased in the median raphe group by the fourth postoperative week. Lastly, lesions in the locus coeruleus dramatically decreased activity in the open field. The results are discussed in regard to the search for specificity of behavioral functions of the distinct ascending monoamine pathways.

Participation of brainstem monoaminergic nuclei in behavioral depression

“…First, however, it should be recognized that while the a motor activity role for NE is supported by a number of reports of behavioral hypoactivity after LC-noradrenergic lesions (Heybach et al, 1978; Owen et al, 1982; Ogren et al, 1983; Britton et al, 1984; Archer and Frediksson, 2003), there are an equal number showing little or no influence (Roberts et al, 1975; Porceddu et al, 1983; Sahakian et al, 1983; Britton et al, 1984; Archer et al, 1986; Sawynok et al, 1995; Neophytou et al, 2001; Srinivasan and Schmidt, 2004) and even some showing increases in baseline or stimulated activity in lesioned animals with high degrees of NE depletion (Ellison, 1975; Mason et al, 1978; 1979; Schwarting and Carey, 1988; Hatip-Al-Khatib and Bolukbasi, 1999; Murrough et al, 2000). These inconsistencies probably reflect inadequate experimental control of the complexities of the noradrenergic systems which possess the same receptors having opposite neural and behavioral functions depending on whether they are located at the LC or in terminal regions, and in which NE release can be affected either independently or concordantly with that of its peptide cotransmitter, galanin, by use of a selective NE-reuptake inhibitor or manipulation of nerve impulse rate, respectively (Stone et al, 2011b).…”

Neurotoxicity of Endocrine Disruptors: Possible Involvement in Brain Development and Neurodegeneration

“…The critical period of sexual differentiation of the brain and behavior in the rat extends from the late fetal stage until the first week after birth (MacLusky and Naftolin 1981), which was the period when the rats were treated with BPA in the study by Kubo and colleagues (2001). Noradrenaline (NA)-containing neurons are densely distributed in the LC, and affect the limbic system, which plays important roles in both open-field behavior and passive avoidance learning (Heybach et al 1978;Chen et al 1992). The morphological changes in the LC induced by BPA ) might therefore be associated with behavioral changes.…”

Interaction of neurotransmitter systems in the hippocampus: a study of some behavioral effects of hippocampal sympathetic ingrowth

“…Depletion of forebrain NE is known to alter responsiveness to novel physical environments and novel objects (Mason et al, 1978) so that animals show less fear than would normally be expected. The literature has been discordant on how NE affects gustatory neophobia (Gallagher and Burwell, 1989), passive avoidance, and open field activity (Heybach et al, 1978;Kimble et al, 1979).…”