Table 3.
Changes in 5-HTergic neuroplasticity in alcohol-preferring rat lines
| Species | Model | Dose of ethanol | Route of administration | BEC | Duration of treatment | Results | Ref # |
| P vs NP rats | Naive | – | – | – | – | Fewer 5-HT-immunostained (5-HT-IM) neurons and reduced 5-HT content in the DRN of P rats | 222 |
| P vs NP rats | Naive | – | – | – | – | Decreased levels of 5-HT and 5-HIAA in the HIP, NAC, and cortex of P rats | 224, 228 |
| P vs NP rats | Naive | – | – | – | – | Reduced density of 5-HT fibres in HIP, caudate-putamen, and hypothalamus of the P. Fewer fine 5-HT fibres in PFC and HIP of P rats | 225-223 |
| P vs NP rats | Naive | – | – | – | – | Lower 5-HT fibre density is in the cingulate and frontal cortices, HIP and hypothalamus of P rats | 226 |
| P vs NP rats | Naive | – | – | – | – | No difference in firing frequencies, the percentages of action potentials in bursts, and the percentages of bursting in P and nP rats, as compared to Wistar rats | 229 |
| P vs NP rats | Naive | – | – | – | – | Higher density of 5-HT1A binding sites in mPFC, parietal, cingulate (20–30%), retrosplenial, occipital and temporal (35–40%), entorhinal cortex (15%) cortices, HIP (10–15%), DRN an MRN (15–20%) in periadolescent and adult P rats | 232, 233 |
| P vs NP rats | Naive | – | – | – | – | Lower 5-HT1B receptor densities in the cingulate and retrosplenial cortices, septum, and AMG of P rats | 235 |
| P vs NP rats | Naive | – | – | – | – | 30% decrease of 5-HT3 binding sites in the AMG of P rats | 236 |
| P vs NP rats | Naive | – | – | – | – | Reduced 5-HT2A binding sites (50–70%) in mPFC, frontal and parietal cortices of P rats | 237 |
| P vs NP rats | Naive | – | – | – | – | 5-HT2 binding sites are reduced in mPFC, frontal, cingulate, parietal, and temporal cortices (–15–25%), NAC, olfactory tubercle, and caudate-putamen (40–50%) of P rats | 238 |
| P vs NP rats | Naive | – | – | – | – | Higher 5HT2C binding sites in the HIP, AMG and the choroid plexus in P rats. Increased 5HT2C receptor coupling in the choroid plexus of P rats | 234 |
| P rats | 2 bottle choice | 10% v/v | Drinking solution | – | 6 or 8 weeks | Microdialysis: Reduced 5-HT extracellular levels (–35%) in the NAC of serotonin following 8 weeks of continuous access to ethanol compared with water controls and animals deprived of ethanol for 2 weeks | 230 |
| P vs NP and Wistar rats. | Injection | 1.0 g/kg | i.p. | – | 5 days. | Decreased basal extracellular 5-HT levels in the NAC of P rats but increased in Wistar and NP rats | 231 |
| P vs NP and Wistar rats. | Injection | 0.5–1.0 g/kg | i.p. | – | Acute | Basal anxiety is elevated in P rats, which is normalized by ethanol pretreatment | 239 |
| sP vs sNP rats | Naive | – | – | – | – | Lower 5-HT and 5-HIAA concentrations in the frontal cortex of sP rats | 243 |
| sP vs sNP rats | Naive | – | – | – | – | Reduced 5-HT2-mediated head dog shake response in sP rats | 245 |
| sP vs sNP rats | Naive | – | – | – | – | Lower 5HT2A binding sites in mPFC, prefrontal and cingulate cortices of sP rats. No significant difference was found in other areas between groups. Reduced head dog shake response to 5-HT2A receptor agonist microinjected into the mPFC in sP rats | 246 |
| sP vs sNP rats | Naive | – | – | – | – | Increased anxiety and higher CRF levels in the AMG in sP rats | 247 |
| sP rats | 2 bottle choice | 10% v/v | Drinking solution | – | Acute | Basal anxiety is elevated in P rats, which is normalized by ethanol pretreatment | 240 |
| sP vs sNP and Wistar rats | 2 bottle choice | 10% v/v | Drinking solution | – | 14 days | Reduced density of 5-HT fibres in the cingulate cortex, the NAC shell and DR but not in the striatum, NAC core, HIP and MR of sP rats | 242 |
| sP vs sNP rats | 2 bottle choice | 10% v/v | Drinking solution | – | 14–15 days | Higher basal anxiety level in ethanol-naïve sP rats, which is normalized by ethanol exposure | 248, 249 |
| FH vs Wistar rats | Naive | – | – | – | – | FH rats have more depressive-like behaviours | 250 |
| FH vs wistar rats | Naive | – | – | – | – | Decrease 5-HT1A induced hypothermia and 5-HT2-induced hyperthermia. No significant difference in the of 5-HT or 5-HIAA levels in the mPFC, HIP hypothalamus and striatum. Decreases 5-HT and 5-HIAA levels in the brain stem with higher 5-HT turnover rate in the hypothalamus, striatum and HIP | 255 |
| FH vs wistar rats | Naive | – | – | – | – | Decreased density of 5-HT1A binding sites in striatum and brainstem and increased density of 5-HT2 binding sites in the striatum and frontal cortex | 256 |
| FH vs Sprague-Dawley rats | Naive | – | – | – | – | Chronic fluoxetine treatment causes hypersensitisation of MR 5-HT1A receptors and desensitisation of hypothalamic 5-HT1A receptor in FH rats | 258 |
| FH vs Sprague-Dawley rats | Naive | – | – | – | – | Increased 5-HT uptake sites in the HIP, brainstem and striatum and decreased 5-HT levels in the brainstem of FH rats. Higher density of 5-HT2C receptors in the cortex of FH rats | 260 |
| FH vs WKY rats | 2 bottle choice | 5% v/v | Drinking solution | – | 28 days of followed by 24 to 48 hrs of withdrawal | Increased SERT expression in the NAC, lateral septum ventral pallidum and VTA of alcohol-na:ive FH rats. Increased density of 5-HT1A receptors in the frontal and parietal occipital and temporal cortices and HIP. No change in 5-HT3 receptor binding. Chronic ethanol consumption decreases 5-HT1A binding in the frontal and parietal cortices but increases binding in the entorhinal cortex and HIP. Hippocampal 5-HT1A binding returns to the levels of ethanol-naive rats following withdrawal | 257 |
| FH/Wjd vs ACI/N rats | 2 bottle choice | 10% v/v | Drinking solution | – | 6 weeks | FH rats have more depressive-like behaviours | 254 |
| FH/Wjd vs ACI/N rats | 2 bottle choice | 10% v/v | Drinking solution | – | 2 weeks | Reduced 5-HT3 in PFC, HIP and AMG of FH/Wjd rats. The anxiolytic effect of 5-HT3 receptor blockade is lost in FH/Wjd rats | 259 |
Abbreviations: NAC, nucleus accumbens; VTA, ventral tegmental area; AMG, amygdala; BLA, basolateral amygdala; LA, lateral amygdala; HIP, hippocampus; PFC, prefrontal cortex; mPFC, medial prefrontal cortex; DR, dorsal raphe; MR, median raphe; TPH, tryptophan hydroxylase; EDC, ethanol derived calories.