ABSTRACT
Neurochemical and behavioral studies in the rat have provided evidence for the view that galanin impairs learning via an inhibitory modulation of cholinergic neurons in the septohippocampal projection, believed to be important for learning and memory. To test this hypothesis, galanin was microinjected via a unilateral chronic cannula located in MS/dBB of rats. Infusion of galanin in the MS/dBB, which contains a high number of 125I-galanin binding sites, did not impair spatial acquisition or memory. On the contrary, spatial acquisition tended to be facilitated by 1 and 3 nmoles of galanin, while the 0.3 nmol dose had no effect. Intraseptal injections of scopolamine (10 microg/rat), a non-specific muscarinic antagonist, also failed to alter learning performance. In contrast, co-injections of galanin (3 nmol) and scopolamine (10 microg) resulted in a marked impairment of spatial acquisition. The effect of intraseptal galanin on basal acetylcholine release in the ventral hippocampus was examined by in vivo microdialysis and high-performance liquid chromatography. Both galanin (3 nmol/rat) and scopolamine (10 microg/rat) infused into the MS/dBB increased basal acetylcholine release in the ventral hippocampus. The combined injections of galanin and scopolamine resulted in an excessive increase in acetylcholine release. These results indicate, that galanin activates septohippocampal cholinergic neurons, suggesting that septal galanin may have a facilitatory role in spatial learning. Moreover, the level of muscarinic activity within the septal area appears to be critical for the effects of galanin on cognitive functions, since the combination of galanin and scopolamine produced a marked impairment in spatial learning, despite a marked increase in hippocampal acetylcholine release. In summary, a limited range of cholinergic muscarinic transmission may contribute to optimal hippocampal function, a finding that has important implications for therapeutic approaches in the treatment of disorders of memory function.
Subject(s)
Acetylcholine/physiology , Galanin/physiology , Hippocampus/physiology , Septal Nuclei/physiology , Space Perception/physiology , Animals , Galanin/pharmacology , Maze Learning/drug effects , Maze Learning/physiology , Memory/drug effects , Memory/physiology , Microdialysis , Muscarinic Antagonists/pharmacology , Rats , Scopolamine/pharmacology , Septal Nuclei/drug effects , Space Perception/drug effectsABSTRACT
The cholinergic neurons in the septohippocampal projection are implicated in hippocampal functions such as spatial learning and memory. The aim of this study was to examine how septohippocampal cholinergic transmission is modulated by muscarinic inputs and by the neuropeptide galanin, co-localized with acetylcholine (ACh) in septohippocampal cholinergic neurons, and how spatial learning assessed by the Morris water maze test is affected. Muscarinic inputs to the septal area are assumed to be excitatory, whereas galanin is hypothesized to inhibit septohippocampal cholinergic function. To test these hypotheses, compounds were microinjected into the medial septum and hippocampal ACh release was assessed by microdialysis probes in the ventral hippocampus of the rat. Blockade of septal muscarinic transmission by intraseptal scopolamine increased hippocampal ACh release suggesting that septal cholinergic neurons are under tonic inhibition. Stimulation of septal muscarinic receptors by carbachol also increased hippocampal ACh release. Despite this increase, both scopolamine and carbachol tended to impair hippocampus-dependent spatial learning. This finding also suggests a revision of the simplistic notion that an increase in hippocampal ACh may be facilitatory for learning and memory. Galanin infused into the medial septum enhanced hippocampal ACh release and facilitated spatial learning, suggesting that septal galanin, contrary to earlier claims, does not inhibit but excites septohippocampal cholinergic neurons. Galanin receptor stimulation combined with muscarinic blockade in the septal area resulted in an excessive increase of hippocampal ACh release combined with an impairment of spatial learning. This finding suggests that the level of muscarinic activity within the septal area may determine the effects of galanin on hippocampal cognitive functions. In summary, a limited range of cholinergic muscarinic transmission may contribute to optimal hippocampal function, a finding that has important implications for therapeutic approaches in the treatment of disorders of memory function.
Subject(s)
Acetylcholine/metabolism , Cognition/drug effects , Galanin/metabolism , Hippocampus/metabolism , Receptors, Muscarinic/metabolism , Septum of Brain/metabolism , Animals , Carbachol/administration & dosage , Cholinergic Agonists/administration & dosage , Cognition/physiology , Galanin/administration & dosage , Hippocampus/drug effects , Immunohistochemistry , Injections, Intraventricular , Ligands , Male , Maze Learning/drug effects , Maze Learning/physiology , Microdialysis , Microinjections , Motor Activity/drug effects , Motor Activity/physiology , Muscarinic Antagonists/administration & dosage , Rats , Rats, Sprague-Dawley , Receptors, Muscarinic/drug effects , Scopolamine/administration & dosage , Septum of Brain/drug effectsABSTRACT
Eighty-six patients with ureteral colic were included in a randomised, prospective, double-blind study of the analgesic efficacy and tolerance of ketoprofen versus diclofenac, both administered intramuscularly. There were no significant differences regarding pain-relief or side-effects.
