Rats selectively bred for high and low swim-test activity show differential responses to dopaminergic drugs

Rationale: Selective breeding of Sprague-Dawley rats has been used to gener ate a line of animals with very low swim-test activity (SwLo) in an attempt to model certain characteristics of depression. For comparison with the Sw Lo animals, a line bred for high swim-test activity (SwHi) and a non-select ively bred line (SwNS) have been generated. Previous studies using these li nes suggested an inverse relationship between dopamine (DA) function in the brain and inactivity in the swim test. Objectives: The current experiments investigated the possibility that SwLo and SwHi rats show differences in c entral DA processes, as suggested by responsiveness to DA agonists. Results : The increase in ambulation produced by D-amphetamine (0.25-1.0 mg/kg) was largest in SwHi rats and smallest in SwLo rats, with SwNS rats showing an intermediate response. Amphetamine levels in plasma and brain tissue were s imilar in SwHi and SwLo rats, indicating that pharmacokinetic differences w ere not responsible for the behavioral differences. Repeated amphetamine ad ministration produced enhancement in the ambulation-increasing effects of t his drug (i.e., sensitization), with significant enhancement seen in all th ree lines. Apomorphine in doses that stimulate postsynaptic receptors (0.25 -4.0 mg/kg) produced mainly increased sniffing behaviors in SwHi and SwNS r ats and oral behaviors in SwLo rats, suggesting that the lines differ in pr oportions of D1, D2, and D3 postsynaptic receptors. Conclusions: The findin gs suggest that DA function differs in lines of rats selectively bred for d ifferences in swim behavior, a feature that may make these lines useful for studying certain depressive symptoms that might be related to DA function.