Cocaine-induced reward enhancement measured with intracranial self-stimulation in rats bred for low versus high saccharin intake

Abstract

Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well-established model of drug abuse vulnerability, with HiS rats being more likely to consume sweets and cocaine (Carroll et al. 2002) than LoS rats. Still, the nature of these differences is poorly understood. This study examined whether the motivational consequences of cocaine exposure are differentially expressed in HiS and LoS rats by measuring intracranial self-stimulation (ICSS) thresholds following acute injections of cocaine (10 mg/kg). Reductions in ICSS thresholds following cocaine injection were greater in HiS rats than in LoS rats, suggesting that the reward enhancing effects of cocaine are greater in the drug-vulnerable HiS than LoS rats. Higher cocaine-induced reward, indicated by lower ICSS thresholds, may explain the higher rates of drug consumption in sweet-preferring animal models, providing a clue to the etiology of cocaine addiction in vulnerable populations.

Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments

“…Consistent with the histamine findings, in other studies, adult rats had more severe withdrawal effects than adolescent rats ( 232 , 233 ). This was in contrast to findings that adolescent rats self-administering cocaine were more sensitive to the rewarding effects of drug ( 52 , 120 ) and showed more severe relapse effects than adult rats ( 18 ). These findings highlight opposite effects that can occur in groups of rats when considering the rewarding vs. aversive effects as previously discussed by Riley ( 234 ), and they emphasize the importance of considering individual differences in vulnerability to drug abuse and response to treatment.…”

“…( 22 , 25 , 26 , 28 )]. In a recent study in our laboratory, the findings of SACC preference predicting drug self-administration were extended to other measures of reward, such ICSS, and HiS rats showed more cocaine-induced reward enhancement of intracranial self-stimulation than LoS rats ( 120 ). Converging results from many of these studies suggest that avidity for sweets and drug-taking behaviors are closely related, heritable, and substitutable ( 22 , 25 , 114 ), and they likely operate through common neural mechanisms [e.g., Ref.…”

Acupuncture Modulates Intracranial Self-Stimulation of the Medial Forebrain Bundle in Rats

“…In the second experiment, cocaine facilitated ICSS response and reduced the ICSS thresholds and M 50 values ( Figure 3 ). These data parallel other findings; cocaine enhanced the brain stimulation reward [ 7 , 24 , 25 , 26 ]. In contrast, HT7 acupuncture did not alter the threshold-lowering effects of cocaine, indicating that HT7 stimulation does not affect the reward-facilitating effects of cocaine.…”

Methamphetamine self-administration in a runway model of drug-seeking behavior in male rats

“…For example, human users of cocaine describe an initial state of energy and euphoria followed in time by a “crash” that is characterized by feelings of anxiety craving and agitation (e.g., Anthony et al, 1989; Gawin and Ellinwood, 1988; Williamson et al, 1997). These dual positive and negative effects of the drug have also been observed in animal studies where cocaine is readily self-administered (Ettenberg et al, 1982; Foltin and Fischman, 1994; Goeders, 1988; Roberts et al, 1977; Wolverton, 1992), produces conditioned place preferences (Bardo, et al, 1995; Ettenberg, 2004; Mueller and Stewart, 2000; Mucha et al, 1982; Tzschentke, 1998), and reduces the threshold for rewarding brain stimulation (Ahmed et al 2002; Radke et al, 2016). In contrast, cocaine has also been shown to produce enhanced anxiety in a variety of tests including the elevated plus maze (Rogerio and Takahashi, 1992; Yang et al, 1992; Ben-Shahar et al, 2008), acoustic startle test (Willick and Kokkinidis, 1995), and in conditioned taste aversion studies (Goudie et al, 1978).…”