Food consumption and weight gain after cessation of chronic amphetamine administration

Highlights

• Overeating and weight gain during recovery from addiction are clinical concerns.

• It is unclear whether this is unique to humans or if it can be modeled in animals.

• Rats received amphetamine or saline for 9 days, followed by abstinence.

• Drug-treated rats gained more weight and consumed more chow than saline-treated rats.

• Drug-induced increases in weight and eating may reflect sensitization processes.

Abstract

Cessation of drug use often coincides with increased food consumption and weight gain in recovering addicts. However, it is not known whether this phenomenon (particularly the weight gain) is uniquely human, or whether it represents a consequence of drug cessation common across species. To address this issue, rats (n = 10/group) were given systemic injections of D-amphetamine (3 mg/kg) or an equal volume of saline vehicle for 9 consecutive days. Beginning 2 days after the final injection, rats were given free access to a highly palatable food mixture (consisting of sugar and butter) along with their standard chow diet, and food consumption and body weight were measured every 48 h for 30 days. Consistent with clinical observations, amphetamine-treated rats showed a greater increase in body weight over the course of the 30 days relative to vehicle-treated rats. Surprisingly, there was no difference in highly palatable food consumption between amphetamine- and vehicle-treated groups, but the amphetamine-treated group consumed significantly more standard chow than the control group. The finding that a history of chronic amphetamine exposure increases food consumption is consistent with previous work in humans showing that withdrawal from drugs of abuse is associated with overeating and weight gain. The current findings may reflect amphetamine-induced sensitization of mechanisms involved in reward motivation, suggesting that weight gain following drug cessation in humans could be due to similar mechanisms.

Introduction

Cessation of drug abuse following a period of chronic intake is associated with hyperphagia and weight gain (Edge & Gold, 2011), which can cause adverse health outcomes beyond those directly associated with drug consumption. It is not known, however, whether this problem is unique to humans (e.g., due to the social contexts or constraints of drug abstinence) or whether it reflects a more fundamental neurobiological consequence of drug cessation. With respect to the latter notion, chronic exposure to drugs of abuse in animal models causes long-lasting neuroadaptations which can persist well beyond the period of drug exposure (Volkow et al, 2002, Volkow et al, 2004). For example, psychostimulant administration can lead to enhanced locomotor responses to these drugs (locomotor sensitization), as well as increased self-administration of other drugs of abuse (Avena, Hoebel, 2003, Hubbell et al, 1993, Liguori et al, 1997, Nichols et al, 1991, Volpicelli et al, 1991). Furthermore, chronic drug exposure can cause persistent increases in behavior directed toward non drug rewards, including palatable foods (so-called “incentive sensitization”) (Gisabella et al, 2009, Mendez et al, 2009, Roesch et al, 2010, Roesch et al, 2009, Taylor, Jentsch, 2001, Wyvell, Berridge, 2001). For instance, chronic amphetamine administration can cause an increase in sugar intake during subsequent abstinence (Avena & Hoebel, 2003) as well as an increase in food consumption stimulated by food-predictive cues (Mendez et al., 2009).

Drugs of abuse act upon the same neural circuitry involved in the motivation to procure and consume food (Volkow, Wang, Fowler, Tomasi, & Baler, 2012). Acute ingestion of highly palatable food (HPF) as well as various drugs, such as amphetamine, alcohol, and cocaine, increase dopamine neurotransmission in the nucleus accumbens (Bassareo, Di Chiara, 1999, Blumenthal, Gold, 2010, Camp et al, 1994, Edge, Gold, 2011, Robinson et al, 1988, Volkow et al, 2012, Wise, Rompre, 1989). Thus, it is no surprise that drug-induced neural changes may result in alterations in appetitive and consummatory behavior, which could result in hyperphagia and ultimately obesity. Notably, however, despite previous demonstrations in animal models that chronic drug (particularly amphetamine) administration can increase appetitive and consummatory behavior during acute test sessions (Avena, Hoebel, 2003, Mendez et al, 2009, Wyvell, Berridge, 2001), it is unclear whether this is reflected in sustained (i.e., home cage) increases in food consumption and, ultimately, in increases in body weight. Given the behavioral and neurobiological overlaps between drug use and food consumption, elucidating their interactions may have considerable implications for understanding drug abuse and comorbid hyperphagia and weight gain during withdrawal. To this end, we investigated the effects of a regimen of chronic amphetamine administration on both consummatory behavior and weight gain for a 30 day period following amphetamine cessation.