Substance P and neurokinin levels are decreased in the cortex and hypothalamus of alcohol-preferring (P) rats

Objective: Central tachykinin levels (i.e., substance P [SP], neurokinin A [NKA], neurokinin B [NKB] and neurokinin K [NKK]) have been reported to fluctuate in association with stress and anxiety Ethanol can also modulate stress and anxiety Further, ethanol intake can change as a result of stress and anxiety. This suggests possible interactions between ethanol and central tachykinins, i.e., changing tachykinin levels could influence ethanol intake and vice versa. However. to date few studies have assessed the potential relationship between tachykinin levels in the brain and ethanol preference. The present study was designed to determine if rodent lines selectively bred for differences in alcohol preference (i.e., alcohol-preferring [P] and nonpreferring [NP] rats) have different tachykinin levels in the brain. Method: Tissue samples from the brains of ethanol-naive P and NP rats were collected from the frontal cortex, caudate, hippocampus, amygdala and hypothalamus. Using radioimmuno assays, concentrations of SP-like immunoreactivity (SP-LI) and neurokinin-like immunoreactivity (NK-LI, i.e., neurokinin A, B and K) in P and NP rats were determined. Results: In P rats, SP-LI was significantly lower in the frontal cortex (F = 12.80, 1/26 df, p = .001) while NK-LI was significantly lower in the frontal cortex (F 7.36, 1/26 df, p = .0 12) and hypothalamus (F = 5.32, 1/26 df, p = .029) compared with NP rats. Conclusions: These data indicate that endogenous SP and neurokinin levels are reduced in discrete brain regions of P rats compared with NP rats. These decreases may be associated with decreased serotonergic innervation of these brain regions in P rats compared with NP rats.