Amphetamine lowers brain stimulation reward (BSR) threshold in alcohol-preferring (P) and non-preferring (NP) rats: Regulation by D₁ and D₂ receptors in the nucleus accumbens.

Abstract

Differences in the mesolimbic dopamine (DA) pathway that regulates alcohol preference may also increase sensitivity to the reinforcing effects of other drugs of abuse. In the present study, the curve-shift (rate-frequency) paradigm was used to quantify the interaction of amphetamine with the rewarding effects of lateral hypothalamic brain stimulation reward (BSR) in alcohol-preferring (P) and -nonpreferring (NP) rats. The role of D-sub-1 and D-sub-2 DA receptors of the nucleus accumbens (NAcc) in mediating the reward-potentiating effects of amphetamine was also determined. Animals were tested with randomly administered amphetamine (0.25, 0.75, 1.25 mg/kg ip), DA-receptor antagonists (SCH 23390 [2.0 microg, 5.0 microg]; eticlopride [2.0 microg, 5.0 microg]), or a combination of the 2 (SCH 23390 [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine; eticlopride [2.0 microg, 5.0 microg] + 0.75 mg/kg amphetamine). Amphetamine produced comparable dose-related leftward shifts in the rate-frequency function for both P and NP rats, with a greater than 60% reduction observed in BSR threshold. On intervening days, baseline threshold was unaltered between tests and similar between rat lines. Unilateral infusion in the NAcc of either the D-sub-1 or D-sub-2 receptor antagonist produced rightward shifts in the rate-frequency function of amphetamine, completely reversing-attenuating its reward-enhancing effects. The results demonstrate that amphetamine produces similar threshold-lowering effects in both P and NP rats and that the reward-potentiating effects of amphetamine do not correlate with alcohol preference under the conditions of the present study.

Responding for brain stimulation reward in the bed nucleus of the stria terminalis in alcohol‐preferring rats following alcohol and amphetamine pretreatments

“…Also, while not statistically significant, the 5.0 mg dose of SCH 23390 did mildly reverse the reduction in EF 50 seen with amphetamine alone. Recent work from our laboratory shows similar effect of SCH 23390 on amphetamine potentiated BSR reward in the MFB (Eiler et al, 2006). These data are consistent with a recent study single-unit recording study by Cheer et al (2005) that demonstrates that SCH 23390 attenuates neural activity in the NAC during intracranial self-stimulation in the MFB.…”

Activation of Dopamine Receptors in the Nucleus Accumbens Promotes Sucrose-Reinforced Cued Approach Behavior

“…Fourth, our observation that D1 and D2 agonists have very similar effects that are the opposite of the effects of D1 and D2 antagonists has important implications for conclusions about the specificity of the drugs' effects. In most previous studies, microinjected D1 and D2 antagonists had very similar behavioral (Hiroi and White, 1991 ; Ozer et al, 1997 ; Koch et al, 2000 ; Yun et al, 2004b ; Eiler et al, 2006 ; Pezze et al, 2007 ; Lex and Hauber, 2008 ; Liao, 2008 ; Nicola, 2010 ; Shin et al, 2010 ; Haghparast et al, 2012 ; Steinberg et al, 2014 ) and electrophysiological (du Hoffmann and Nicola, 2014 ) effects. Because the concentration of injected antagonists required to observe effects is much higher than the binding constants of these drugs for their target receptors, the similarity of D1 and D2 antagonist effects calls into question their specificity: it is possible that the drugs either bind to the same dopamine receptor, or to a third receptor class that is not a dopamine receptor at all.…”

Qualitative differences between C57BL/6J and DBA/2J mice in morphine potentiation of brain stimulation reward and intravenous self-administration

“…All of the C57 mice learned to turn the wheel and reached criteria within the first session whereas the successful DBA mice on average took longer to reach the same criteria. Previous studies in inbred or selectively bred mouse or rat strains have generally either not found or not described differences in the rate of learning an operant for brain stimulation reward (Cazala and Cardo 1977; Cazala et al 1974; Cazala and Guenet 1979; Eiler et al 2007; Eiler et al 2006; Eiler et al 2005; Garrigues and Cazala 1983; Ranaldi et al 2001; Woods et al 2003; Zacharko et al 1990). The delay seen in the DBA mice is not the result of a general learning deficit since DBA mice learn to lever press (water training prior to i.v.…”