Gastrectomy alters emotional reactivity in rats: neurobiological mechanisms

Abstract

Gastrectomy (Gsx) is associated with altered emotional function and a predisposition to depression/anxiety disorders. Here we investigated the effects of Gsx on emotional reactivity in rats and explored the underlying neurobiological mechanisms. Gsx- and sham-operated rats were exposed to behavioural tests that explore anxiety- and depression-like behaviour (open field, black and white box, elevated plus maze, social interaction, forced swim) as well as memory (object recognition). The potential neurobiological mechanisms underlying these differences were explored by measuring (i) turnover of candidate neurotransmitter systems in the nucleus accumbens, (ii) hippocampal neurogenesis by BrdU labelling or by analysis of candidate genes involved in neuronal growth and (iii) changes in mRNA expression of candidate genes in dissected hippocampal and amygdala tissue. Data from individual behavioural tests as well as from multivariate analysis revealed differing emotional reactivity between Gsx- and sham-operated rats. Gsx rats showed reduced emotional reactivity in a new environment and decreased depression-like behaviour. Accumbal serotonin and dopamine turnover were both reduced in Gsx rats. Gsx also led to a memory deficit, although hippocampal neurogenesis was unaffected. Of the many candidate genes studied by real-time RT-PCR, we highlight a Gsx-associated decrease in expression of Egr-1, a transcription factor linked to neural plasticity and cognition, in the hippocampus and amygdala. Thus, Gsx induces an alteration of emotional reactivity and a memory/cognitive deficit that is associated with reduced turnover of serotonin and dopamine in the nucleus accumbens and decreased expression of Egr-1 in the hippocampus and amygdala.

Fig. 1

Behavioural parameters of sham-operated (n=10) and Gsx rats (n=6) in the open field during the 10-min test period. Columns and bars represent mean ± SEM. *P <0.05.

Fig. 2

Behavioural parameters of sham-operated (n=10) and Gsx rats (n=6) in the forced swim test during (A) the three triads of the first day, (B) the 15 min of the first day and (C) the first 5 min of the 15 min pre-test session at the first day and during the test phase (5 min) on the second day. *P <0.05, ***P<0.001 Gsx vs. sham; ^♦P<0.05, ^♦♦♦P <0.001 when comparing day 1 and 2 for each surgical group.

Fig. 3

Distribution of sham-operated/Gsx rats along the two first factors extracted with the principal components analysis. Factor 1 was represented by the horizontal axis and accounts for 27.25% of the total variance. Factor 2 was represented by the vertical axis and accounts for 20.82% of the total variance. This principal components analysis was based on the behavioural results obtained in the open field (number of rearings at the periphery, number of line crossings, number of groomings), the black and white box (number of rearings in the white compartment, number of groomings), the elevated plus maze (number of rearings in the closed arms, percentage of entries into the open arms, percentage of time spent in the central zone) and in the forced swim test (immobility during the first triad, struggling during the second triad, time spent swimming the second day).

Fig. 4

Time spent exploring during the recognition trial of the object recognition test. Rats from the sham group spent more time exploring the new object whereas rats from the Gsx gruop spent the same time exploring the old and new object. Sham, n=9; Gsx group, n=5. ***P<0.001.

Fig. 5

Effects of Gsx on hippocampal mRNA expression of adipor1 (adiponectin receptor 1), insulin receptor (insr), Egr-1 (early growth response protein 1), Trh (thyrotropin-releasing hormone) and Galr3 (galanin receptor 3) in comparison with sham-operation. P<0.05 for all comparisons.