ABSTRACT
1. We examined the effect, in rats, of an intraseptal microinjection of fasciculin (FAS), an irreversible peptide acetylcholinesterase (AChE) inhibitor, on a) AChE activity measured in septum and hippocampus, b) 3H-quinuclidinyl benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepam (3H-FNZ) binding to hippocampal benzodiazepine receptors as a control for QNB and OXO binding, d) acquisition and retention in three different behavioral paradigms, i.e., water-finding (in which there is concomitant habituation to the apparatus), step-down inhibitory avoidance, and shuttle avoidance. 2. AChE activity in septum decreased 2 days (-66%) and 5 days (-48%) after FAS microinjection; a slight reduction (-35%) occurred in the dorsal hippocampus on day 2 (P less than 0.05; N = 6 per group); no changes in AChE activity were observed in ventral hippocampus on day 2 or day 5. 3. No changes in 3H-QNB, 3H-OXO, or 3H-FNZ binding constants were demonstrable in the hippocampus either 2 or 5 days after intraseptal FAS administration. 4. No changes in training or test session performance in any of the three behavioral situations were observed 2-3 days after the intraseptal microinjection of FAS. 5. The persistent inhibition of septal AChE caused by FAS microinjection into the septum is not sufficient to induce major changes either in hippocampal cholinergic muscarinic receptors, or in the learning or retention of behaviors regulated by the septum and/or hippocampus.
Subject(s)
Behavior, Animal/drug effects , Cholinesterase Inhibitors/pharmacology , Elapid Venoms/pharmacology , Hippocampus/enzymology , Septal Nuclei/enzymology , Animals , Avoidance Learning/drug effects , Biological Assay , Cholinesterase Inhibitors/administration & dosage , Hippocampus/drug effects , Male , Microinjections , Radioligand Assay , Rats , Rats, Inbred Strains , Septal Nuclei/drug effectsABSTRACT
We examined the effect, in rats, of an intraseptal microinjection of fasciculin (FAS), an irreversible peptide acetylcholinesterase (AChE) inhibitor, on a)AChE activity measured in septum and hippocampus, b)3H-quinuclidiny benzylate (3H-QNB) and 3H-oxotremorine (3H-OXO) binding to hippocampal cholinergic muscarinic receptors, c) 3H-flunitrazepan (3H-FNZ) binding to hippocampal benzodiazepine receptors as a control for QNB and OXO binding, d) acquisition and retention in three different behavioral paradigms, i. e., water-finding (in which there is concomitant habituation to be apparatus), step-down inhibitory avoidance, and shuttle avoidance. AChE activity in septum decreased 2 days (-66%) and 5 days (-48%) after FAS microinjection; a slight reduction (-35%) occurred in the dorsal hippocampus on day 2 (P<0.05; N=6 per group); no changes in AChE activity were observed in ventral hippocampus ion day 2 or day 5. No changes in 3H-QNB, 3H-OXO, or 3H-FNZ binding constants were demonstrable in the hippocampus either 2 or 5 days after intraseptal FAS adminstration. No changes in training or test session performance in any of the three behavioral situations were observed 2-3 days after the intraseptal microinjection of FAS. The persistent inhibition of septal AChE caused by FAS microinjection into the septum is not sufficient to induce major changes either in hippocampal cholinergic muscarinic receptors, or in the learning or retention of behaviors regulated by the septum and/or hippocampus
Subject(s)
Animals , Rats , Male , Behavior, Animal/drug effects , Cholinesterase Inhibitors/pharmacology , Elapid Venoms/pharmacology , Analysis of Variance , Avoidance Learning/drug effects , Biological Assay , Cholinesterase Inhibitors/administration & dosage , Elapid Venoms/administration & dosage , Hippocampus/drug effects , Microinjections , Radioligand Assay , Septal Nuclei/drug effectsABSTRACT
1. The mechanisms of the supersensitivity to cholinergic drugs after chronic haloperidol was studied in normal and parasympathectomized submandibular glands of the rats. 2. Both parasympathectomy and haloperidol treatment for 7 days (2 mg/kg/day, i.p.) increased the sialogogue response of the glands to methacholine, a cholinomimetic drug. 3. Both denervation and haloperidol administration induce up-regulation of the muscarinic receptors as expressed per gram of the tissue. 4. Haloperidol causes no further increase in sensitivity than denervation alone. 5. These data demonstrate that secretory supersensitivity to cholinergic drugs in the rat submandibular glands, after chronic haloperidol and parasympathectomy is related to an increase in muscarinic cholinergic receptors.
