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Aims: Cocaine abuse remains an important public health issue. This study was designed to test how the short-acting KOP-r antagonist tetrapeptide [D-Trp]CJ-15,208 (cyclo[Phe-d-Pro-Phe-d-Trp]) affects cocaine self-administration (SA), cocaine-induced locomotor activity and food intake. Methods: (1) Male C57/BL6 mice acquired cocaine SA (0.5mg/kg/infusion, FR1) for 7 consecutive days. Half of the mice were injected with [D-Trp]CJ-15,208 (20mg/kg, s.c.) and half were injected with vehicle before cocaine SA daily for 7 days. (2) To determine the effect of [D-Trp]CJ-15,208 on cocaineinduced locomotor activity, mice were injected with either compound or vehicle before cocaine injection (15mg/kg, i.p.) and locomotor activities were recorded. (3) To assess the effect of [DTrp]CJ-15,208 on food intake, mice were injected with compound or vehicle and the amount of food consumed over a 2-h period was measured. Results: (1) Mice injected with [D-Trp]CJ-15,208 had attenuated cocaine SA compared to controls. (2) Mice pre-treated with [D-Trp]CJ-15,208 did not differ in their locomotor activity either before or after cocaine injection compared to controls. (3) Mice injected with [D-Trp]CJ-15,208 before food exposure did not differ in their food intake from controls. Conclusions: These studies show that [D-Trp]CJ-15,208 produced a decrease in daily cocaine SA in mice. This effect of [D-Trp]CJ-15,208was neither due to a decrease in cocaine-induced locomotor activity nor accompanied by decreases in food intake. These data support future studies of short-acting compounds with KOP-r antagonist effects as potential pharmacotherapeutic approaches against cocaine addiction. Financial support: NIH-NIDA 1R01DA029147-01A1 (YZ), NIHNIDA 1R01DA032928-01 (JA) and NIH-NIDA P60 DA05130 (MJK).

Aims: Cocaine abuse remains an important public health issue. This study was designed to test how the short-acting KOP-r antagonist tetrapeptide [D-Trp]CJ-15,208 (cyclo[Phe-d-Pro-Phe-d-Trp]) affects cocaine self-administration (SA), cocaine-induced locomotor activity and food intake. Methods: (1) Male C57/BL6 mice acquired cocaine SA (0.5mg/kg/infusion, FR1) for 7 consecutive days. Half of the mice were injected with [D-Trp]CJ-15,208 (20mg/kg, s.c.) and half were injected with vehicle before cocaine SA daily for 7 days. (2) To determine the effect of [D-Trp]CJ-15,208 on cocaineinduced locomotor activity, mice were injected with either compound or vehicle before cocaine injection (15mg/kg, i.p.) and locomotor activities were recorded. (3) To assess the effect of [DTrp]CJ-15,208 on food intake, mice were injected with compound or vehicle and the amount of food consumed over a 2-h period was measured. Results: (1) Mice injected with [D-Trp]CJ-15,208 had attenuated cocaine SA compared to controls. (2) Mice pre-treated with [D-Trp]CJ-15,208 did not differ in their locomotor activity either before or after cocaine injection compared to controls. (3) Mice injected with [D-Trp]CJ-15,208 before food exposure did not differ in their food intake from controls. Conclusions: These studies show that [D-Trp]CJ-15,208 produced a decrease in daily cocaine SA in mice. This effect of [D-Trp]CJ-15,208was neither due to a decrease in cocaine-induced locomotor activity nor accompanied by decreases in food intake. These data support future studies of short-acting compounds with KOP-r antagonist effects as potential pharmacotherapeutic approaches against cocaine addiction. Financial support: NIH-NIDA 1R01DA029147-01A1 (YZ), NIHNIDA 1R01DA032928-01 (JA) and NIH-NIDA P60 DA05130 (MJK).

Using the open field, for making an overall assessment of behavioural change in response to acetaldehyde (AcH) treatment, the results from the present study demonstrate that AcH produces behavioural and physiological effects similar to those of ethanol. High doses of AcH produced a similar degree of change as high doses of ethanol. Both compounds render the animal incapable of locomotor activities, such as ambulation and rearing and both produce a decrease of 2–3 °C in body temperature. AcH, however, appears to be a much more potent compound as behavioural and physiological changes are exhibited even after a dose of 10 mg/kg, while the dose of ethanol necessary to produce a decrease in open-field behaviour is at least 10 times as much. Females were more sensitive to the effects of AcH at the 100 mg/kg dose.