ACTH1-24 effects on d-amphetamine self-administration and the dynamics of brain dopamine in rats.

ABSTRACT

Experiments aimed at determining the neural basis of reward have previously focused on the role of neurotransmitters and have only recently begun to investigate the role of peptides. The present experiment investigated the effect of ACTH1-24 on d-amphetamine self-administration in rats. Animals were trained daily (8 hour sessions) to press a lever which activated a system that administered 0.125 mg/kg of intravenous amphetamine. After achievement of a stable self-injection frequency, subjects were injected SC with 10, 20 or 40 micrograms/80 microliters ACTH1-24 immediately prior to placement in the apparatus. The 20 micrograms and 40 micrograms doses of the peptide fragment induced a statistically significant attenuation of d-amphetamine self-injection which lasted for 2 days. Control rates of responding were achieved by 5 to 10 days after the peptide treatment. An experiment was conducted to evaluate possible neuromodulatory effects of the peptide fragment. Twenty-four hr after ACTH1-24, HVA was elevated in the caudate. When both apomorphine and ACTH1-24 were administered, the combination lowered HVA in the caudate to a greater degree than apomorphine alone. The peptide fragment, when combined with haloperidol, attenuated the haloperidol-induced increases of DOPAC and HVA in both the caudate and nucleus accumbens. It was tentatively concluded that the neuromodulatory action of ACTH1-24 on dopaminergic neurons may result in an increase in the rewarding quality of d-amphetamine, thus rendering control level self-infusions superfluous.(ABSTRACT TRUNCATED AT 250 WORDS)