Effect of isolation rearing on pre- and post-synaptic serotonergic function in the rat dorsal hippocampus.
Several behavioural, neurochemical, and structural alterations found in isolation-reared rats are similar to those in human schizophrenia. This study investigated changes in cholinergic and serotonergic function in the hippocampus following isolation rearing. Rats were reared in social isolation from weaning for 6 weeks before study and compared to group-reared rats. An in vitro electrophysiological study investigated the effect of isolation rearing on postsynaptic 5-HT(1A) function on CA1 hippocampal neurones activated with the muscarinic agonist carbachol and found no change in the sensitivity of these postsynaptic receptors between the groups. However, a change in presynaptic function was identified, as there was a significant reduction in the time taken for neuronal firing to recover to 50% of the original rate following 5-HT (10 microM) application, in isolation compared to group-reared rats. These data suggest a possible change in reuptake following isolation. Uptake studies using (3)[H]5-HT, however, found no change in the inhibition of uptake produced by either fluoxetine or paroxetine in isolation compared to group-reared rats. The selective 5-HT(1B) antagonist CP-294253 (1 microM), increased endogenous 5-HT release from hippocampal slices in vitro and this effect was greater (P < 0.001) in group compared to isolation-reared rats. These results indicate that the change in presynaptic 5-HT neuronal function was due to impaired autoreceptor responsiveness. Carbachol (1 microM) increased the firing rate of all neurones recorded but only a proportion of these showed a concentration-related increase. Isolation rearing increased the sensitivity of neurones, showing a concentration-related increase in firing in response to carbachol, but had no effect on the other neurones. In summary, the present study showed that isolation rearing alters presynaptic 5-HT(1B) but not postsynaptic 5-HT(1A) receptor activity in the hippocampus. Isolation rearing in the rat results in hippocampal dysfunction, including reduced serotonergic and enhanced muscarinic activity of some neurones. These effects may in part underlie the behavioural consequences of isolation relevant to human developmental disorders.
Muchimapura
Suparporn
S
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, England.
Mason
Robert
R
Marsden
Charles A
CA
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012934:Social Isolation; D013569:Synapses / Q000378:metabolism*
D018679:Cholinergic Agonists; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D012701:Serotonin; D017374:Paroxetine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002217:Carbachol