ABSTRACT
The authors examined the effects of activity wheel running (AWR) and propranolol on contextual fear conditioning (CFC) and messenger RNA (mRNA) for galanin (GAL) in the locus coeruleus (LC) and brain-derived neurotrophic factor (BDNF) in the hippocampal formation (HF) in rats. Freezing behavior during the testing session of the CFC protocol was elevated in the AWR-placebo group compared to sedentary-placebo and AWR-propranolol groups. AWR increased GAL mRNA in the LC. CFC increased BDNF mRNA in the HF. These results suggest that exercise enhances CFC and that antagonism of the beta-adrenoreceptors attenuates this effect. The exercise-related induction of GAL gene expression in the LC may influence noradrenergic transmission to facilitate CFC.
Subject(s)
Adrenergic beta-Antagonists/pharmacology , Brain-Derived Neurotrophic Factor/metabolism , Conditioning, Psychological/drug effects , Fear , Galanin/metabolism , Propranolol/pharmacology , Analysis of Variance , Animals , Autoradiography/methods , Behavior, Animal , Brain-Derived Neurotrophic Factor/genetics , Corticosterone/blood , Electroshock/adverse effects , Freezing Reaction, Cataleptic/drug effects , Galanin/genetics , Gene Expression Regulation/drug effects , In Situ Hybridization/methods , Male , Motor Activity/drug effects , RNA, Messenger/metabolism , Radioimmunoassay/methods , Rats , Rats, Long-Evans , Running , Time FactorsABSTRACT
Affective disorders and substance abuse frequently coexist, yet few previous studies have examined drug self-administration using animal models of depression. The olfactory-bulbectomized rat is a well-established model that exhibits a high degree of neurochemical similarity to depression. Olfactory bulbectomy (OBX) increases dopamine receptor densities in the ventral striatum, which may increase the reinforcing effects of drugs of abuse. Experiments were designed to test the hypotheses that acquisition and stable self-administration of amphetamine would be increased in bulbectomized rats. In the first experiment, rats underwent bilateral OBX or sham surgery and intravenous jugular catheters were implanted 12-14 days later. Acquisition was examined using a standard operant paradigm involving a nose-poke response for a very low dose of D-amphetamine sulfate (12 microg/infusion, IV). A separate group of rats received coinfusions of sulpiride. In a second experiment designed to minimize differences in acquisition and examine stable self-administration, lever pressing for a low (0.10 mg/kg, IV) or high (0.25 mg/kg, IV) dose of D-amphetamine sulfate was measured in rats pretrained to lever press for food. Bulbectomized rats acquired the self-administration of very low dose amphetamine faster than sham-operated rats and this effect was reversed by sulpiride coinfusion. Stable self-administration of the low dose of amphetamine was also markedly increased in bulbectomized rats. The findings reveal the utility of the OBX model for studying the neurobiological basis of depression and drug abuse comorbidity and support the hypothesis that neurochemical abnormalities associated with depression may enhance the addictive properties of some drugs of abuse.
