Russell Amato - Academia.edu (original) (raw)

Papers by Russell Amato

Effects of GABAA Modulators in Rats Responding Under A Differential Reinforcement of Low Rates (DRL) Schedule

The Faseb Journal, Apr 1, 2010

Effects of pregnanolone on the retention of tandem response sequences in male rats

The Faseb Journal, Apr 1, 2009

Effects of chronic ethanol on ketamine-induced disruptions in learning in rhesus monkeys

Alcoholism Clinical and Experimental Research

Partial mGlu5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects

Neuropsychopharmacology, 2015

Cocaine abuse remains a public health concern for which pharmacotherapies are largely ineffective... more Cocaine abuse remains a public health concern for which pharmacotherapies are largely ineffective. Comorbidities between cocaine abuse, depression and anxiety support the development of novel treatments targeting multiple symptom clusters. Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor 5 (mGlu5) subtype are currently in clinical trials for the treatment of multiple neuropsychiatric disorders and have shown promise in preclinical models of substance abuse. However, complete blockade or inverse agonist activity by some full mGlu5 NAM chemotypes demonstrated adverse effects, including psychosis in humans and psychotomimetic-like effects in animals, suggesting a narrow therapeutic window. Development of…

ACS Chemical Neuroscience, 2013

Cocaine is a powerful and highly addictive stimulant that disrupts the normal reward circuitry in... more Cocaine is a powerful and highly addictive stimulant that disrupts the normal reward circuitry in the central nervous system (CNS), producing euphoric effects. Cocaine use can lead to acute and life threatening emergencies, and abuse is associated with increased risk for contracting infectious diseases. Though certain types of behavioral therapy have proven effective for treatment of cocaine addiction, relapse remains high, and there are currently no approved medications for the treatment of cocaine abuse. Evidence has continued to accumulate that indicates a critical role for the metabotropic glutamate receptor subtype 5 (mGlu 5 ) in the modulation of neural circuitry associated with the addictive properties of cocaine. While the small molecule mGlu 5 negative allosteric modulator (NAM) field is relatively advanced, investigation into the potential of small molecule mGlu 5 NAMs for the treatment of cocaine addiction remains an area of high interest. Herein we describe the discovery and characterization of a potent and selective compound 29 (VU0463841) with good CNS exposure in rats. The utility of 29 (VU0463841) was demonstrated by its ability to attenuate drug seeking behaviors in relevant rat models of cocaine addiction.

Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats

Alcohol (Fayetteville, N.Y.), Jan 6, 2015

The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehyd... more The present study compared two putative pharmacotherapies for alcohol abuse and dependence, dehydroepiandrosterone (DHEA) and pregnanolone, with two Food and Drug Administration (FDA)-approved pharmacotherapies, naltrexone and acamprosate. Experiment 1 assessed the effects of different doses of DHEA, pregnanolone, naltrexone, and acamprosate on both ethanol- and food-maintained responding under a multiple fixed-ratio (FR)-10 FR-20 schedule, respectively. Experiment 2 assessed the effects of different mean intervals of food presentation on responding for ethanol under a FR-10 variable-interval (VI) schedule, whereas Experiment 3 assessed the effects of a single dose of each drug under a FR-10 VI-80 schedule. In Experiment 1, all four drugs dose-dependently decreased response rate for both food and ethanol, although differences in the rate-decreasing effects were apparent among the drugs. DHEA and pregnanolone decreased ethanol-maintained responding more potently than food-maintained ...

Pharmacology Biochemistry and Behavior, 2011

Behavioural Pharmacology, 2010

Relatively little is known about the behavioral effects of the neurosteroids compared with other ... more Relatively little is known about the behavioral effects of the neurosteroids compared with other drugs that modulate the γ-aminobutyric acid A (GABA A ) receptor complex. This study examined the acute effects of pregnanolone and dehydroepiandrosterone (DHEA) in male rats responding under a differential-reinforcement-of-low-rate schedule of reinforcement. For comparison, three positive modulators of the GABA A receptor (lorazepam, ethanol, and pentobarbital), one negative modulator (β-CCM), and one neutral modulator (flumazenil) were tested. Pregnanolone was also administered in combination with DHEA to test for antagonism between these substances. Pregnanolone, lorazepam, and pentobarbital produced increases in responding at intermediate doses, and ethanol and pentobarbital produced decreases in responding at the highest doses tested. However, all four drugs dose-dependently decreased reinforced responding by decreasing interresponse times. DHEA, β-CCM, and flumazenil did not increase responding at intermediate doses or decrease reinforced responding. DHEA did not competitively antagonize the disruptive effects of pregnanolone. In summary, pregnanolone and DHEA produced effects on differentialreinforcement-of-low-rate responding that are similar to other positive and negative GABA A modulators, respectively, and do not produce these effects through a single binding site.

Behavioural Pharmacology, 2012

Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxi... more Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectively for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanoland food-maintained responding, compared to control, while also decreasing blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than foodmaintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared to food-maintained responding, and it decreased BECs as ethanolmaintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, while not affecting ethanol-maintained responding compared to control. Low to intermediate doses of rauwolscine produced small, non-significant increases in ethanolmaintained responding and BECs. Chlordiazepoxide produced significant decreases in foodmaintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence.

Alcoholism: Clinical and Experimental Research, 2012

Background-To address the hypothesis that GABA A receptor modulation during adolescence may alter... more Background-To address the hypothesis that GABA A receptor modulation during adolescence may alter the abuse liability of ethanol during adulthood, the effects of adolescent administration of both a positive and negative GABA A receptor modulator on adult alcohol intake and preference were assessed.

Advances in Pharmacological Sciences, 2011

Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five ... more Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABA A receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will also present data collected by our laboratory showing that one neurosteroid in particular, dehydroepiandrosterone (DHEA), decreases ethanol intake in rats under a variety of conditions. In the process, we will also mention relevant studies from the literature suggesting that both particular subtypes and subunits of the GABA A receptor play an important role in mediating the interaction of neurosteroids and ethanol.

Differential effects of chronic alcohol on GABA(A)- and NMDA-receptor mediated disruptions in learning in rhesus monkeys

The Faseb Journal, Apr 1, 2007