Submitted to: Behavioural Brain Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 30, 2013
Publication Date: September 15, 2013
Citation: Dennis, R.L., Lay Jr, D.C., Cheng, H. 2013. Effects of early serotonin programming on behavior and central monoamine concentrations in an avian model. Behavioural Brain Research. 253:290-296. Interpretive Summary: Serotonin, a neurotransmitter targetted by antidepresents such as paxil, is vital during brain development. Serotonin enhancing antidepressents are sometimes prescribed for post-partum depression and have been shown to pass via breast milk. The present study investigates the long-term effects of increased serotonin during the first two days post-hatch, using a chicken model for postnatal exposure. Chicks were exposed to either a low or high dose of serotonin agonist, or saline control. Birds exposed to low dose postnatal exposure expressed greater fearfulness and aggressiveness than either control or high dose birds. Memory was slightly inhibited in low dose birds, while high dose birds showed a greater inhibition of memory. The neurotransmitter serotonin was decreased in the adult brain of birds treated with a low dose of serotonin agonist following hatch, but not those treated with high doses. A key serotonin receptor in the brain associated with aggressive behaviors (serotonin 1A receptor), was shown to increase in birds from low dose treatment groups only. The present findings are evidence of long term effects on behavior and brain development due to early exposure to serotonin altering pharmaceuticals that are highly dose dependent. Our study also highlights the potential of using avian models, such as chickens, for investigating the impacts of serotonin altering pharmaceuticals on brain development and behavior without the confounding influences of maternal effects.
Technical Abstract: Serotonin (5-HT) acts as a neurogenic compound in the developing brain; however serotonin altering drugs such as SSRIs are often prescribed to pregnant and lactating mothers. Early agonism of 5-HT receptors could alter the development of serotonergic circuitry, altering neurotransmission and behaviours mediated by 5-HT signaling, including memory, fear and aggression. This study was designed to investigate the effects of early serotonin agonism on later behaviors. An extremely aggressive White leghorn strain (15I5) was used in the study. The chicks were injected with 5-MT (a serotonin agonist) at 2.5 mg/kg (low dose), 10 mg/kg (high dose) or saline (control) on the day of hatch and a second dose 24 h later (n=12/trt). Chicks’ fear response and memory were tested at 2 wks of age. In the fear test, chicks were subjected to a social isolation test for 20 min, time to first vocalization and numbers of vocalizations were recorded. In the memory test, chicks were placed in a running wheel and presented with an imprinted object (white box with a red light) and a similar shaped novel object (blue box with a white light), respectively. The distance traveled in the wheel toward each object was measured. At 10 wks of age birds were tested for aggression and concentrations of catecholamines were determined from the raphe nucleus and hypothalamus (n=12). Both high and low dose chicks tended to have shorter latency to first vocalization and a greater number of vocalizations compared with control chicks (P<0.10 and P<0.05, respectively). Memory test showed that chicks from all groups traveled a similar distance toward a familiar object. However, control chicks walked the least toward a novel object, low dose chicks tended to walk further (P<0.10), and high dose chicks walked significantly further for a novel object (P<0.05). In aggression tests, both high (P<0.10) and low dose (P<0.05) males exhibited greater frequency of aggressive behaviors compared to controls, while no difference in aggression was evident in the females. Norepinephrine concentrations were also reduced in the low dose birds in the hypothalamus (P<0.05) and in the raphe nucleus (P<0.10). Serotonin concentrations tended to be lower only in the both hypothalamus and raphe nucleus of the low dose birds (P<0.10). 5-HT1A expression was greatest in the hypothalamus and raphe nucleus of low dose birds (P<0.05 and 0.10, respectively). The agonism of the serotonin system during neural development of birds genetically predisposed to aggression alters both the dopaminergic and serotonergic systems further increasing their aggressiveness.