Effects of Morphine and Naloxone on Ethanol‐ and Sucrose‐Reinforced Responding in Nondeprived Rats

Abstract

In the following series of experiments, effects of morphine (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) and naloxone (0.1, 0.3, and 1.0 mg/kg) were assessed in nondeprived rats trained to leverpress with 10% ethanol, sweetened ethanol, or 5% sucrose and water as the reinforcers. Morphine, at doses of 0.1, 0.3, and 1.0 mg/kg had little effect on responding with ethanol or sweetened ethanol available on a fixed ratio 4 (FR4) schedule of reinforcement, but at the 3.0 mg/kg dose, morphine suppressed responding to near zero. Similar results were obtained when 10% ethanol and water were available on a concurrent FR4 FR4 schedule of reinforcement. When 5% sucrose and water were available concurrently, morphine suppressed responding at 3.0 and 10 mg/kg. Naloxone (0.1, 0.3, and 1.0 mg/kg) decreased responding for ethanol, sweetened ethanol, and sucrose solutions in a dose-dependent manner. Naloxone decreased total number of responses/session by shortening the duration of responding without affecting momentary rate. Overall, the data suggest that the endogenous opioid system plays a role in the ability of ethanol to reinforce operant behavior. However, this role does not appear to be specific to ethanol because similar results were observed with sucrose reinforcement. Failure to find enhanced ethanol intakes following morphine injections in the operant situation suggests that the method used to measure ethanol self-administration makes a difference in assessing the effects of drugs on ethanol intake.

Effects of Naltrexone and Fluoxetine on Alcohol Self-Administration and Reinstatement of Alcohol Seeking Induced by Priming Injections of Alcohol and Exposure to Stress

“…In STUDY 1, it was found that during the maintenance phase, low doses of naltrexone and fluoxetine decrease lever presses for alcohol. These data are in agreement with previous reports which have shown that preferentially mu opioid receptor antagonists and SSRI agents, at doses similar to the ones used in the present report, decrease alcohol self-administration during the maintenance phase (e.g., Murphy et al 1988: Haraguchi et al 1990Hyytia and Sinclair 1993;Schwarz-Stevens et al 1992; see Amit et al 1991 andUlm et al 1995 …”

Central Opioid Receptors Differentially Regulate the Nalmefene-Induced Suppression of Ethanol- and Saccharin-Reinforced Behaviors in Alcohol-Preferring (P) Rats

“…Thus, opioid receptors within some (eg NACC and VTA), but not all mesolimbic substrates can selectively modulate EtOH-reinforced behaviors. Previous reports in the literature have suggested that a selectivity in reducing EtOH-motivated behaviors in rodents was difficult, equivocal, or not clearly observable (Brown and Holtzman, 1979;Herz, 1997;Schwartz-Stevens et al, 1992;Weiss and Koob, 1991;Weiss et al, 1990). However, we hypothesized that the operant contingencies under which one evaluates opiate receptor antagonists following parenteral or direct administrations into the CNS is a very important factor in observing selective antagonism on EtOH-motivated behaviors.…”

“…The exact neurobiological substrate(s) participating in EtOH's rewarding effects, however, are not well understood, in part because the majority of the preclinical studies using opioid antagonists have been conducted using systemic drug injections (Froehlich and Li, 1993;Herz, 1997;Reid and Hubbell, 1992;Schwartz-Stevens et al, 1992). While it has been assumed that the action of opioid antagonists on EtOH's reinforcing properties are mediated centrally (McBride and Li, 1998), this has only been documented in a few published reports in the literature (Heyser et al, 1999;Hyytiä and Kiianmaa, 1997).…”

“…While a voluminous literature support a role for nonselective and selective opioid antagonists as potential pharmacotherapies in humans, a selective role for opioid mechanisms in alcohol reward is still a matter of debate (Brown and Holtzman, 1979;Herz, 1997;Reid and Hubbell, 1992;Schwartz-Stevens et al, 1992;Weiss and Koob, 1991;Weiss et al, 1990). Some researchers have argued that while both EtOH and other palatable reinforcers are affected by opioid antagonists, the relative magnitude of suppression is far less for water, sucrose, and saccharin solutions (see June et al, 1998June et al, , 1999Heyser et al, 1999).…”

Advances in the Use of Naltrexone an Integration of Preclinical and Clinical Findings

“…Specifically, pretreatment with these opioid receptor antagonists did not eliminate initiation of alcohol drinking or "alcohol sampling" (Hyytia & Kiianmaa, 2001;Schwarz-Stevens, Files, & Samson, 1992;Siviy, Calcagnetti, & Reid, 1982;Stromberg, Mackler, Volpicelli, & O'Brien, 2001). It should be noted, however, that animal and human studies differ with regard to several important factors.…”