PMC

Nicotine blocks PPP. A, Representative traces (left) and plots (right) show that the frequency of mEPSC in MSNs from saline-treated mice was greater than amphetamine self-administering mice but far less than those in nonresponding mice. ^$p<0.05, ^$$p<0.01, ^$$$p<0.001, Student’s t test. B, Compared with saline-treated mice, amphetamine self-administration reduced the frequency of low-amplitude mEPSCs, while the frequency of mEPSCs was broadly higher in nonresponding mice. ^$p<0.05, saline-treated versus amphetamine self-administering mice; ^##p<0.01, saline-treated versus nonresponding mice; Bonferroni t test. Inset, The cumulative mEPSC amplitude distribution was unchanged across groups. C, Frequency distributions (left) and the average peak frequency (right) show a prominent low-frequency distribution of mEPSCs from amphetamine self-administering mice (small arrow) and more broadly distributed firing frequencies in MSNs from nonresponding mice (arrowhead; inset). ^$$p<0.01, ^$$$p<0.001, Student’s t test. D, Responses of individual MSNs from saline-treated mice show that amphetamine, and the addition of nicotine, reduced the frequency of mEPSCs. *p<0.05, paired t test. E, Amphetamine with nicotine or without decreased the frequency of low-amplitude mEPSCs. *p<0.05, Bonferroni t test, amphetamine compared with either vehicle or amphetamine with nicotine. Inset, The mEPSC amplitude distribution was unchanged. F, Frequency distributions (left) and the average peak frequency (right) of mEPSCs from saline-treated mice shows that both amphetamine (arrow) and amphetamine with nicotine (double arrow) increased low-frequency events. G, In MSNs from amphetamine self-administering mice, nicotine blocked the increase in mEPSCs that followed amphetamine. *p<0.05, paired t test. H, Amphetamine augmented the frequency of low-amplitude mEPSCs, but had no effect on their amplitude distribution (inset). *p<0.05, Bonferroni t test, amphetamine compared with either saline or amphetamine with nicotine. I, The distribution (left) and the average peak frequency (right) of mEPSCs from amphetamine self-administering mice show that amphetamine reduces 1–2 Hz activity (arrow). The addition of nicotine moderated the effect of amphetamine by increasing 1–2 Hz activity (double arrows). *p<0.05, paired t test. J, The distribution (left) and average peak frequency (right) show that mEPSCs s from saline-treated mice were similar to those from amphetamine self-administering mice exposed to amphetamine. K, Both amphetamine and amphetamine with nicotine reduced the mEPSC frequency in MSNs from nonresponding mice. *p<0.05, **p<0.01, paired t test. L, Amphetamine and nicotine reduced low-amplitude mEPSCs, but had no effect on their amplitude distribution (inset). *p<0.05, amphetamine compared with either vehicle or amphetamine with nicotine; ^&p<0.01, vehicle compared with either amphetamine or amphetamine with nicotine; Bonferroni t test. M, The frequency distribution (left) and average peak frequency (right) of mEPSCs from nonresponding mice show that amphetamine with (double arrow) or without nicotine (arrow) increases low-frequency events. *p<0.05, paired t test.

Nicotine and amphetamine modify burst and pause activity. A, Nicotine blocked the reduction of discrete burst activity by amphetamine in ChIs from saline-treated mice. For all panels, *p<0.05, **p<0.01, paired t test. B, The burstiness of ChIs from saline-treated mice was unaffected by amphetamine or the coadministration of nicotine. C, Amphetamine with nicotine or without did not change discrete pausing or (D) pause strings in ChIs from saline-treated mice. E, In ChIs from amphetamine self-administering mice, amphetamine or coadministered nicotine did not modify discrete bursting (F) but nicotine increased the length of bursting. G, Nicotine blocked the increase in discrete pausing by amphetamine in ChIs from amphetamine self-administering mice. H, In ChIs from amphetamine self-administering mice, an amphetamine challenge produced a nicotine-dependent enhancement of pause strings by boosting the intra-pause frequency and the percentage of time spent pausing.

Effects of argon on amphetamine-induced changes in locomotor activity and mu receptor activity in the nucleus accumbens. (A) When challenged with amphetamine, rats pretreated with amphetamine and argon had lower locomotor activity than rats pretreated with amphetamine and air (AA); in contrast, no significant difference in locomotor activity was found between rats pretreated with saline and argon and those pretreated with saline and air when challenged with amphetamine (SA) or saline (SS). This indicates that argon blocked locomotor sensitization to amphetamine, but had effect neither on locomotor activity induced by acute amphetamine nor on basal locomotor activity. Locomotor activity is expressed in arbitrary units. (B) As assessed immediately after being challenged with amphetamine, rats pretreated with amphetamine and argon had reduced mu receptor activity compared to rats pretreated with amphetamine and air (AA); in contrast, no significant difference in mu receptor activity was found between rats pretreated with saline and argon and those pretreated with saline and air when challenged with amphetamine (SA) or saline (SS). This indicates that argon blocked the increase in mu receptor activity induced by repeated amphetamine, but had effect neither on the increase in mu receptor activity induced by acute amphetamine nor on basal mu receptor activity. The ratio of the dissociation constant (Kd) to the maximal number of binding sites (Bmax) was calculated to assess the activity of mu receptors in the nucleus accumbens; mu receptor activity in controls rats pretreated and challenged with amphetamine was taken as a 100 % value. SS: pretreatment with saline + challenge with saline; SA: pretreatment with saline + challenge with saline; AA: pretreatment with amphetamine + challenge with amphetamine. * P < 0.001 vs AA + Air.

Effects of argon on amphetamine-induced changes in locomotor activity and mu-receptor activity in the nucleus accumbens. (a) When challenged with amphetamine, rats pretreated with amphetamine and argon had lower locomotor activity than rats pretreated with amphetamine and air (AA); in contrast, no significant difference in locomotor activity was found between rats pretreated with saline and argon and those pretreated with saline and air when challenged with amphetamine (SA) or saline (SS). This indicates that argon blocked locomotor sensitization to amphetamine, but had effect neither on locomotor activity induced by acute amphetamine nor on basal locomotor activity. Locomotor activity is expressed in arbitrary units. (b) As assessed postmortem immediately after being challenged with amphetamine, rats pretreated with argon and repeated administration of amphetamine (AA) had reduced mu-receptor constitutive activity in the nucleus accumbens (as estimated by the ratio of Bmax to Kd) compared with rats pretreated with air; in contrast, argon had effect on mu-receptor activity neither in rats pretreated with saline solution and challenged with amphetamine (SA) nor in control rats pretreated and challenged with saline solution (SS). This indicates that argon blocked the increase in mu-receptor activity induced by repeated administration of amphetamine, but had no effect on basal mu-receptor activity and acute amphetamine-induced changes in mu-receptor activity. Opioid mu-receptor activity in control rats pretreated and challenged with amphetamine was taken as a 100% value. Data are given as the median value±25th–75th percentiles; n=7–8 per condition. *P<0.05; **P<0.001. AA, pretreatment+challenge with amphetamine; SA, pretreatment saline+challenge amphetamine; SS, pretreatment+challenge with saline.