Medial septal lesions in rats enhance locomotor sensitization to amphetamine.
BACKGROUND
The mesolimbic dopamine (DA) system appears to play a major role in the locomotor activating and sensitizing effects of several addictive drugs. However, less is known about the neural structures that may modulate this system.


OBJECTIVE
We examined the effects of medial septal lesions on the locomotor activating and sensitizing effects of amphetamine in between-subjects (experiment 1) and within-subjects (experiment 2) experiments.


RESULTS
Repeated injections of 0.6 mg/kg (experiment 1) or 1.0 mg/kg (experiment 2) amphetamine over six sessions produced more locomotion in the lesioned rats than in the sham-operated controls. This repeated exposure to amphetamine subsequently increased the locomotor response to 0.2 mg/kg (experiment 2) and 0.4 mg/kg (both experiments) amphetamine in the lesioned rats, such that these sensitized, lesioned rats moved more in response to these doses than unsensitized, lesioned rats and sensitized controls did. Both experiments also indicated that this prior sensitization enhanced the locomotor response to 0.4 mg/kg amphetamine more in the lesioned rats than in the control rats when compared with the response produced by saline following sensitization or by the same dose of amphetamine prior to sensitization. In contrast, prior exposure to amphetamine decreased the locomotor response to 4.0 mg/kg amphetamine in the lesioned rats (experiment 1).


CONCLUSIONS
Although medial septal lesions occasionally enhance locomotor responses to moderate doses of amphetamine prior to sensitization, a main effect of these lesions is to further enhance the effects of locomotor sensitization to amphetamine. Implications for drug addiction are discussed.
Kelsey
J E
JE
Department of Psychology, Bates College, Lewiston, ME 04240, USA. jkelsey@bates.edu
Grabarek
J A
JA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D020318:Rats, Long-Evans; D012686:Septal Nuclei / Q000502:physiology*
D015259:Dopamine Agents; D000661:Amphetamine; D004298:Dopamine