Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.
Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.
Cannizzaro
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C
Dipartimento di Scienze Farmacologiche, Università di Palermo, V. Vespro 129, 90127 Palermo, Italy. psyco@unipa.it
Plescia
F
F
Gagliano
M
M
Cannizzaro
G
G
Mantia
G
G
La Barbera
M
M
Provenzano
G
G
Cannizzaro
E
E
D008735:5-Methoxytryptamine / Q000008:administration & dosage / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D004357:Drug Synergism; D004873:Ergolines / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012737:Sex Factors; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism