Reduced Sensitivity to Ethanol Reward, But Not Ethanol Aversion, in Mice Lacking 5=HT_1B Receptors

Abstract

Various serotonergic receptor systems are thought to influence the motivational effects of ethanol. This experiment characterized the acquisition of ethanol-induced conditioned taste aversion and ethanol-induced conditioned place reference in mutant knockout mice lacking 5-HT1b receptors. In the taste conditioning procedure, adult homozygous knockout mice (-/-) and homozygous wild-type mice (+/+) received access to 0.2 M NaCl solution, followed immediately by intraperitoneal injection of 0 to 4 g/kg of ethanol. Ethanol produced dose-dependent conditioned taste aversion that was the same in both genotypes. In the place conditioning procedure, knockout and wild-type mice received six pairings of a tactile stimulus with ethanol (2 g/kg, i.p.). A different tactile stimulus was paired with saline. Ethanol produced increases in locomotor activity, with wild-type mice showing higher levels of ethanol-stimulated activity than knockout mice during conditioning trials 5 and 6. Wild-type mice demonstrated conditioned place preference for the ethanol-paired stimulus. In contrast, knockout mice showed no evidence of place conditioning. These results are generally consistent with an important role for serotonergic systems in ethanol reward and specifically indicate that 5-HT1b receptors are important for ethanol's rewarding effects but not for ethanol's aversive effects.

Sex-Dependent Modulation of Ethanol Consumption in Vesicular Monoamine Transporter 2 (VMAT2) and Dopamine Transporter (DAT) Knockout Mice

“…Ethanol-preferring rats display alterations in tissue serotonin levels (McBride et al, 1990Aulakh et al, 1994;Zhou et al, 1994), responses to serotoninergic agents (Gudelsky et al, 1985;Aulakh et al, 1988aAulakh et al, , b, 1992Aulakh et al, , 1994Wang et al, 1988), serotonin reuptake (Arora et al, 1983;Hulihan-Giblin et al, 1993;Chen and Lawrence, 2000), and serotonin receptor densities (Hulihan-Giblin et al, 1992Wong et al, 1993;McBride et al, 1994McBride et al, , 1997Chen and Lawrence, 2000). A variety of serotonergic agents can reduce voluntary ethanol consumption in animal models and in humans (for a review, see Lovinger, 1999;Myrick et al, 2001), and serotonin receptor gene KOs also affect ethanol self-administration (Crabbe et al, 1996;Risinger et al, 1996Risinger et al, , 1999Risinger et al, , 2000Rubinstein et al, 1997;El-Ghundi et al, 1998;Phillips et al, 1998).…”

“…Animal models also support a role for dopaminergic differences in the genetic determination of ethanol reward. Rats bred for ethanol preference display dopamine receptor (Stefanini et al, 1992;McBride et al, 1993) and forebrain dopamine levels different from ethanol nonpreferring rats (Zhou et al, 1995), and dopamine receptor gene knockouts (KOs) also alter ethanol self-administration (Crabbe et al, 1996;Risinger et al, 1996Risinger et al, , 1999Risinger et al, , 2000Rubinstein et al, 1997;El-Ghundi et al, 1998;Phillips et al, 1998).…”

Place Conditioning: What Does It Add to Our Understanding of Ethanol Reward?

“…There are also substantial differences in place conditioning across standard inbred strains (Cunningham et al, 1996) and recombinant inbred strains (Cunningham, 1995). Moreover, recent studies have shown that this procedure is able to detect differences produced by targeted gene mutation (e.g., Risinger et al, 1996Risinger et al, , 2001. Of the more than six dozen genotypes that have been examined over the last 12 years, nearly 75% have been found to show CPP with EtOH.…”

“…However, more recent articles suggest that this effect is modest at best (Bouwknect et al, 2000;Crabbe et al, 1999;Risinger et al, 1999b). 5-HT1B knock-out mice were not able to acquire signifi cant CPP to EtOH but readily demonstrated the acquisition of EtOH-induced conditioned taste aversion (Risinger et al, 1996).…”

Role of Medial Prefrontal Cortical Group II Metabotropic Glutamate Receptor in the Development of Cocaine Sensitization

“…This procedure not only permits assessment of the conditioning of drug reinforcement but also can provide indirect information regarding the positive and negative reinforcing effects of drugs (Tzschentke 1998). Many laboratories are now using this technique to study the subjective properties of drugs because CPP studies are much easier to conduct than intravenous self-administration studies (Risinger et al 1996;Carlezon et al 1998;Tzschentke 1998).…”