Rats selectively-bred for behavior related to affective disorders: proclivity for intake of alcohol and drugs of abuse, and measures of brain monoamines.

Several lines of rats potentially useful for studying affective disorders have been developed in our laboratory though selective breeding for behavioral characteristics. The propensity of these lines to consume alcohol and other drugs of abuse (amphetamine and cocaine) was examined. Also, measurement of the concentration of brain monoamines - norepinephrine, dopamine, and serotonin - as well as estimation of their metabolism by measurement of the major extracellular metabolites of these monoamines was carried out to examine possible relationships of brain chemistry to the behavioral characteristics shown by these lines, as well as to their propensity for drug usage. The lines of rats are: Swim Low-active (SwLo) and Swim High-active (SwHi), which show either very low (SwLo) or very high (SwHi) amounts of motor activity in a swim test; Swim-test Susceptible (Susceptible or SUS) and Swim-test Resistant (Resistant or RES), which are highly susceptible (SUS) or highly resistant (RES) to having their swim-test activity depressed by being exposed to a stressful condition prior to the swim test; and Hyperactive (HYPER), which show spontaneous nocturnal hyperactivity compared to non-selectively bred (i.e., normal) rats as well as both extreme hyperactivity and behavioral depression after being exposed to a stressful condition. Regarding alcohol and drug usage, SUS rats readily consume alcohol while all other lines including non-selected, normal rats do not, and SwLo rats show a strong tendency to consume amphetamine and cocaine. Marked differences in brain monoamines were found between the various lines and normal rats, with salient differences seen in norepinephrine, particularly in the hippocampus, and in dopamine in forebrain regions (striatum and nucleus accumbens).

Depletion of brain norepinephrine does not reduce spontaneous ambulatory activity of rats in the home cage.

6-Hydroxydopamine (6-OHDA) lesions of brain noradrenergic neurons and terminals were made in rats to assess the importance of forebrain norepinephrine (NE) for mediating circadian patterns of spontaneous ambulatory activity that rats show in the home cage. 6-OHDA was injected intracranially into the fibers of the ascending noradrenergic dorsal and ventral bundle pathways or infused into the lateral ventricle or both. Rats living in a 12/12 h light/dark cycle exhibit a marked increase in ambulatory activity during the dark period in comparison to the light period and a 'W-shaped' pattern of activity during the 12 h of the dark phase. Results showed that near-total depletion of brain NE did not impair the capacity to generate normal patterns of spontaneous ambulatory activity that occur in the home cage. In the animals that sustained the most complete NE lesions, the amounts of activity generated at times of peak activity were exaggerated in comparison to the control animals, which is consistent with the possibility that NE in the brain exerts a moderating influence on behavior.

Motor activation by amphetamine infusion into nucleus accumbens core and shell subregions of rats differentially sensitive to dopaminergic drugs.

Selective breeding based on activity in a swim test has been used to produce lines of rats that show a high level of activity in the swim test (Swim High-active (SwHi) rats) and a low level of activity in the swim test (Swim Low-active (SwLo) rats). Previous studies have indicated that dopamine (DA) function is enhanced in SwHi rats and reduced in SwLo rats; a principal finding was that SwLo rats showed much smaller increases in ambulatory activity after systemic administration of amphetamine than did SwHi or non-selected rats. In light of the importance of the nucleus accumbens (NAC) in amphetamine-induced activity, the present study investigated whether DA function in NAC differs in SwHi and SwLo rats. Amphetamine was infused bilaterally into either the core or shell subregion of NAC, and ambulation or swim test activity was then measured. In SwLo rats, infusion of amphetamine (0.2-2.0 microg) into either NAC core or shell produced moderate increases in ambulation. In SwHi rats, infusion of amphetamine into NAC shell produced similar moderate increases in ambulation, but infusion into the core produced markedly larger dose-related increases in ambulation. In the swim test, infusion of amphetamine (1.0 microg) increased activity by affecting the dominant behavior of each line; i.e. struggling increased in SwHi rats and floating decreased in SwLo rats, with large effects seen in both lines with infusion into either NAC core or shell. These results support the idea that the distinct behavioral characteristics of SwHi and SwLo rats are mediated in part by differences in NAC-DA function.

NPY stimulation of food intake in Siberian hamsters is not photoperiod dependent.

Siberian hamsters (phodopus sungorus sungorus) show naturally occurring seasonal cycles of food intake that are triggered by changes in the photoperiod. In long "summer-like" days (LD) food intake is at its peak, whereas in short "winter-like" days (SD) food intake reaches a nadir. Although the mechanisms underlying these changes in food intake are unknown, results from previous studies suggest that the ability to stimulate or inhibit food intake in Siberian hamsters complements the naturally occurring food intake cycle. Thus, inhibitors of food intake are more effective in SDs, whereas stimulators of food intake are more effective in LDs. A stimulator of food intake in a wide variety of species is neuropeptide Y (NPY). Therefore, we explored the ability of NPY to stimulate food intake in Siberian hamsters. In addition, we tested whether the efficacy of NPY to stimulate food intake was photoperiod dependent. In Experiment 1, LD-housed adult male hamsters were given a series of NPY doses (0.078-10.0 micrograms) intracerebroventricularly (ICV) into the third ventricle and food intake was measured 30 min, 1, 2, and 4 h postinjection. NPY was a potent stimulator of food intake with the 7.5 micrograms dose of NPY producing the greatest increase at 30 min. In Experiment 2, adult male hamsters were housed in LDs or SDs and were given various doses of NPY ranging from 0.039-7.5 micrograms. NPY given ICV stimulated food intake to the same degree in LDs as in SDs with the greatest increases in food intake occurring in the hamsters receiving the 2.5 and 5.0 micrograms dose of NPY. In addition, Siberian hamsters were very sensitive to NPY with the lowest effective dose (0.0585 microgram) that stimulated food intake being six times smaller than in other rodents tested. Collectively, these results showed that Siberian hamsters were more sensitive to the stimulatory effect of NPY on food intake than any other species, but that the ability of NPY to stimulate feeding was not photoperiod dependent.