Nonpreferring Rats Research Articles

Contents of monoamines in forebrain regions of alcohol-preferring (P) and -nonpreferring (NP) lines of rats

The contents of monoamine neurotransmitters and metabolites were assayed in the frontal cortex, nucleus accumbens and anterior striatum of rats from the selectively bred alcohol-preferring P and nonpreferring NP lines. Lower levels of serotonin (20–30%) in all three brain regions of P as compared with NP rats lends support to the hypothesis that a decreased metabolic activity and/or innervation by serotonin neurons is associated with the abnormally high volitional intake of ethanol. Of additional interest, however, were the approximately 25% lower contents of dopamine and its major metabolites in the nucleus accumbens of the P rats. This observation may indicate that P rats have a specific deficiency in the dopaminergic projections from the ventral tegmental area to the nucleus accumbens and, since the accumbens is an important structure in brain reward circuitry, it might also be an important determinant of the excessive volitional intake of alcohol by P rats.

Effect of low dose ethanol on spontaneous motor activity in alcohol-preferring and -nonpreferring lines of rats.

To determine if behavioral arousal may be associated with ethanol preference, the effects of low to moderate doses of ethanol on spontaneous motor activity (SMA) were studied in the selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats as well as in the Maudsley Reactive (MR/N) and Nonreactive (MNR/N) strains. Alcohol-naive rats had food and water available ad lib, but food was removed 24 hr before and during activity testing. After an intraperitoneal injection of saline (5 ml) or ethanol (0.12 to 1.5 g/kg), SMA was monitored every three min for 30 min in an electronic activity monitor. The P and MR/N rats exhibited increased SMA after doses of 0.12 and 0.25 g/kg. Both the NP and MNR/N rats failed to show increased SMA at any ethanol dose. Moderate doses of ethanol, 1.0 and 1.5 g/kg, consistently depressed SMA in all lines/strains. In 24 hr-fasted rats, increased SMA occurred within 6-12 min after injection, but free-fed rats exhibited increased SMA 12-24 min after an ethanol dose of 0.25 g/kg. Free-choice drinking scores (10% ethanol (v/v) versus water) for the P, MR/N, MNR/N and NP rats were 6.6 +/- 0.5, 4.9 +/- 0.8, 2.2 +/- 0.7 and 1.4 +/- 0.3 g ethanol/kg body wt/day (mean +/- SEM), respectively. The data indicate a positive relationship between ethanol preference and ethanol-induced motor stimulation and suggest that hyperactivity may be an expression of the positive reinforcing effect of ethanol for alcohol-preferring rats.

Different sensitivities to ethanol in alcohol-preferring and -nonpreferring rats

The sensitivity of the P and NP rats to ethanol was determined by the jumping test [23]. Proper interpretation of this test requires knowledge of the regional differences in the distribution of ethanol as a function of time after ethanol injection. Ethanol concentration in brain was higher than those in tail blood and skeletal muscle within the initial 30 min following the intraperitoneal injection of ethanol and was also higher than that in cerebral blood in the first 15 min. However, after 60 min, ethanol concentrations in brain and tail blood were identical. After ethanol injection (2 g/kg), the P rats jumped 88, 78, 85, 54 and 19% higher than the NP rats at 30, 60, 120, 180 and 240 min, respectively. The tail blood ethanol concentrations did not differ between the P and NP rats after 60 min. The P rats also jumped higher than the NP rats after injection of 1.5 and 2.5 g/kg ethanol. These results indicate that the P rats are innately less sensitive to the effects of ethanol than the NP rats.