Novel Therapy for Nicotine Addiction in Alcohol Dependent Rats

The co-dependence of nicotine and alcohol addiction occurs at high rates, complicates treatment, and is often associated with significant morbidity and mortality. Treatment options of alcohol and tobacco co-dependence are limited. Currently, there are drugs available for nicotine dependence or alcohol dependence. However, there are no therapeutic drugs available on the market for the co-dependence of nicotine and alcohol. Therefore, and important opportunity of new therapeutic options and drug development has presented itself. NT69L, a non-selective neurotensin (NT) agonist, provides a potential novel therapy for nicotine addiction in alcoholics by interacting with the common neurotransmitter circuits supporting the rewarding process for both nicotine and alcohol. Considering the behavioral effects of NT69L in attenuating nicotine self-administration in rats and alcohol consumption in mice, the present study was designed to assess the effects of NT69L as a new drug. NT69L was used in the treatment of nicotine addiction in an animal model of alcoholics and in attempts to attenuate withdrawal signs associated with nicotine and alcohol dependence. Wistar rats pre-exposed to alcohol vapor or air were allowed to self-infuse nicotine (0.03mg/kg/infusion) or saline. When the rats reached a stable level of responding, the effect of pretreatment with NT69L (1mg/kg i.p.) on the reinforcing effect of nicotine was determined. Animals self-infused nicotine at a significantly (p \u3c .05) higher rate compared to saline in both air and alcohol vapor exposed groups. Acute pretreatment with a single injection of NT69L significantly (p \u3c .05) reduced nicotine self-infusion in both the alcohol vapor and the air exposed groups for 5 days post-injection. Additionally, NT69L attenuated the alcohol- and nicotine-induced withdrawal signs associated with the discontinuation of alcohol and nicotine administration. Neurotensin agonist, NT69L, may represent a potential novel therapy to treat the co-addiction of alcohol and nicotine

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine

Neurotensin Agonist Attenuates Nicotine Potentiation to Cocaine Sensitization

Tobacco usage typically precedes illicit drug use in adolescent and young adult populations. Several animal studies suggest nicotine increases the risk for subsequent cocaine abuse, and may be a negative prognostic factor for treatment of cocaine addiction; i.e., a “gateway drug”. Neurotensin (NT) is a 13-amino acid neuropeptide that modulates dopamine, acetylcholine, glutamate, and GABA neurotransmission in brain reward pathways. NT69L, a NT(8-13) analog, blocks behavioral sensitization (an animal model for psychostimulant addiction) to nicotine, and nicotine self-administration in rats. The present study tested the effect of NT69L on the potentiating effects of nicotine on cocaine-induced locomotor sensitization. Male Wistar rats were injected daily for seven days with nicotine or saline (control) followed by four daily injections of cocaine. NT69L was administered 30 min prior to the last cocaine injection. Behavior was recorded with the use of activity chambers. Subchronic administration of nicotine enhanced cocaine-induced behavioral sensitization in Wistar rats, consistent with an hypothesized gateway effect. These behavioral effects of cocaine were attenuated by pretreatment with NT69L. The effect of the neurotensin agonist on cocaine sensitization in the nicotine treated group indicated a possible therapeutic effect for cocaine addiction, even in the presence of enhanced behavioral sensitization induced by nicotine

Association of cerebellar and pre-motor cortex gray matter density with subjective intoxication and subjective response following acute alcohol intake

Abstract Acute alcohol intake produces subjective intoxication (SI) and response (SR; e.g., valanced stimulation and sedation), which has important implications for alcohol-related risk. Individuals who experience less SI may be more likely to engage in risky behaviors while drinking. Gray matter morphometry in brain regions underlying cognitive and affective processes may help to inform individual differences in subjective intoxication and response. The subjective effects of alcohol vary between limbs of the blood alcohol concentration (BAC) curve (i.e., whether BAC is rising or falling; acute tolerance). We examined the relationship between gray matter density (GMD) and SI/SR as a function of BAC limb. Healthy social drinkers (N = 89; 55 women) completed an alcohol challenge paradigm (target BAC = 0.08 g/dL) and structural magnetic resonance imaging (MRI). Participants completed measures of SR and SI on ascending and descending BAC limbs. Association between GMD and SI/SR on each limb were assessed using whole-brain, voxel-wise general linear models. GMD estimates were extracted from significant clusters. Differences in association of GMD and SI/SR between limbs were assessed using hierarchical regression. Significant associations of SI with GMD on the ascending limb were observed in the cerebellum. A significant association between SR and GMD on the descending limb were observed in the pre-motor cortex (BA6) and cerebellum. We identified common and unique associations among cerebellum and pre-central gyrus structures with SI and SR between BAC limbs. Functional imaging studies may further clarify unique dimensions of subjective alcohol effects linked to the observed structural associations