Table 2.
Drug reward effects on PNNs.
| Cocaine | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
|---|---|---|---|---|---|---|---|---|
| Sensitization | ||||||||
| Cocaine sensitization (20 mg/kg), IP | Mice/Male | Adult (8 weeks) | Cerebellum | 1X/day x 6 days every 48 h | 1 month + acute cocaine challenge (10 mg/kg), IP | Sensitized locomotor activity and sniffing | Medial nucleus: ↓ WFA intensity | Vazquez-Sanroman et al., 2015a |
| Cocaine sensitization (20 mg/kg), IP | Mice/Male | Adult (PND 77) | Cerebellum | 1X/day x 6 days every 48 h | 7 days + acute cocaine challenge (10 mg/kg), IP | Sensitized locomotor activity and sniffing | Medial nucleus: ↑ WFA intensity | Vazquez-Sanroman et al., 2015b |
| Cocaine sensitization (15 mg/kg), IP | Rats/Male | Adult | Prefrontal cortex (PFC): Prelimbic (PL) and infralimbic (IL) | 1X or 5X daily | 2 or 24 h | Sensitized locomotor activity | 1 Day: PFC-PL and IL: ↓ WFA intensity 2 h later; IL: ↑ WFA intensity 24 h later | Slaker et al., 2018 |
| 5 Day: PFC-PL and IL: ↑ WFA intensity 2 h later | ||||||||
| Conditioned place preference (CPP) | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Cocaine CPP (20 mg/kg), IP | Mice/Male | 7 weeks | Cerebellum | 1X/day alternating, 8 days total | 1 day after preference test (2 days after last cocaine) | Subset shows CPP = Preference (PREF) group | Golgi cells: ↑ WFA intensity in PREF group; DCN cells: ↓ WFA intensity in all cocaine groups independent of preference | Carbo-Gas et al., 2017 |
| Cocaine CPP (15 mg/kg), IP | Rats/Male | Adult | Cerebellum | 1X/day alternating, 8 days total | 90 min after preference test (2 days after last cocaine) | IL mPFC lidocaine infusion increased cocaine CPP | Golgi cells: ↑ WFA intensity in after IL mPFC lidocaine treatment during training days | Guarque-Chabrera et al., 2022 |
| Cocaine CPP (12 mg/kg), IP | Rats/Male | Adult | Prefrontal cortex (PFC): Prelimbic (PL) | 3X/day alternating | 30 min, 2 h, 24 h | CPP | No change in WFA intensity; Decreased PV intensity at all time points | Jorgensen et al., 2020 |
| Self-administration | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Cocaine self-administration (0.3 mg/infusion), IV | Rats/Male | Adult | Cerebellar cortex: (vermis and hemispheres) | 2 h/day X 7 days; half given 1 h/day (ShA) or 6 h/day (LgA) X 20 days | 1, 7, or 28 days abstinence | 6 h vs 1 h access escalated cocaine intake | ↑ WFA intensity with abstinence in ShA and LgA rats 1 Day | Sanchez-Hernandez et al., 2021 |
| ↓ WFA intensity vs. naïve in ShA 28 days | ||||||||
| ↑ WFA intensity vs. naïve in LgA rats | ||||||||
| Cocaine self-administration (0.75 mg/kg/infusion), IV | Rats/Male | Adult | Prefrontal cortex (PFC): anterior cinglulate; ventral or dorsal prelimbic (v or dPL); ventral infralimbic (IL), insular, ventral orbitofrontal (vOFC), lateral orbitofrontal (lOFC) | 6 h/day X 10 days | 1 or 30 days abstinence | Self-administration | 1 Day: PFC-dPL, vPL, IL: ↑ number of WFA cells dependent on level of WFA intensity and hemisphere 30 Days: No changes | Roura-Martinez et al., 2020 |
| Ethanol | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Ethanol (2.5 g/kg), SC | Mice/Male & Female | PND 7 | Barrel cortex | 2X injection, 2 h apart at PND 7 | 7 days or 83 days | Barrel cortex: PND 14: ↑ number of WFA cells in L4/5; PND 90: ↑ number of WFA cells not co-labeled with PV; ↓ number of PV/WFA cells; | Saito et al., 2019 | |
| Hippocampus: dentate gyrus (DG) | Hippocampus-DG: PND90: ↓ number of WFA cells | |||||||
| Ethanol (2.5 g/kg), SC | Mice/Male & Female | PND 7 | Hippocampus: CA1/CA3 | 2X injection, 2 h apart at PND 7 | 83 days | Decreased contextual fear conditioning; Increased fragmentation of slow-wave sleep; hyperactivity | Retrosplenial cortex: ↓ number of WFA cells | Lewin et al., 2018 |
| Retrosplenial cortex | ||||||||
| Ethanol, drinking-in-the dark procedure (20% ethanol vs. water) | Mice/Male | 8 weeks | Insular cortex and primary motor cortex | 4 h/day xX 4 days/week for 1 week or 6 weeks | 20 h | Alcohol self-administration | Insular cortex: ↑ WFA, aggrecan, brevican, and phosphacan intensity at 6 weeks | Chen et al., 2015 |
| Ethanol (5 g/kg, 25% ethanol) | Mice/Male | 28–37 days | Prefrontal cortex: Orbitofrontal cortex (OFC) | Ethanol (intragastic) 6 days between PND 28–37 | 73 days | Decreased reversal learning on Barnes maze; Decreased center time in open field | PFC-OFC: ↑ WFA, brevican, and neurocan intensity | Coleman et al., 2014 |
| Ethanol (25, 50, or 75 mM) or intragastric (5.25 g/kg) | Rats/Male | 21 days | Primary cortical astrocytes or hippocampus or intragastric treatment 2X at PND 4–9 | 1 day | 0 days | Cortical and hippocampal cultures: ↓ arylsulfatase B activity; ↑ C4S; ↑ cellular and medium neurocan mRNA and protein in cortical cultures; Hippocampus in vivo ethanol: ↑ neurocan | Zhang et al., 2014a | |
| Ketamine | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Ketamine (30 mg/kg), IP | Mice/Male | Not specified | Hippocampus: CA1 | 7 daily | 1 day | Increased locomotion; decreased prepulse inhibition with low-intensity stimulus | Hippocampus-CA1 (so and sp), Basket cells: ↓Total PV + and Cat-315 + /PV + cells; Axoaxonic cells: ↓ total PV + and Cat-315-/PV + cells; O-LM/H-S* cells: ↓ total PV + , Cat-315 + /PV + , and Cat-315-/PV + , cells; Bistratified (so): ↓ PV + and Cat-315-/PV + cells | Fujikawa et al., 2021 |
| Ketamine (30 mg/kg), IP | Rats/Male | Adult (8 weeks) | Prefrontal cortex (PFC) | 5 daily/2 d off/5 daily/2 d/12 d isolation/2 d social interaction test | 2 days | Decreased non-aggressive social interaction | PFC: ↓ number of WFA cells; no change in number of PV cells or double-labeled WFA/PV cells | Matuszko et al., 2017 |
| Hippocampus: CA1 | Hippocampus-CA1: No change in WFA cell number or dendrite intensity of WFA | |||||||
| Ketamine (30 mg/kg), IP | Rats/Male | Adult (8 weeks) | Prefrontal cortex (PFC) | 5 daily/2 d off/5 daily/2 d/12 d isolation/2 d social interaction test | 2 days | PFC: PV + cells: ↓ WFA-labeled unit area; fine structure analysis: ↑ number but smaller, less circular WFA-labeled units | Kaushik et al., 2020 | |
| Ketamine (100 mg/kg)/xylazine (10 mg/kg)/acepromazine (3 mg/kg), IP (KXA) | Mice/Male & Female | Adult (8–12 weeks) | Somatosensory cortex: S1 | 1X, 2X, 3X, 6X; once every 72 h | 4 h | 3X KXA, every 2 days; Increased ocular dominance plasticity in layer 4 of V1 after brief (3 d) monocular deprivation | S1: ↓ percent of WFA-coated cells after 2–6 injections; | Venturino et al. 2021 |
| Nicotine | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Nicotine self-administration (0.03 mg/kg/infusion), IV | Rats/Male | Adult | Prefrontal cortex: Orbitofrontal cortex (OFC) | 1 h/day X at least 21 days | 45 min or 3 days | Self-administration | PFC-OFC: ↓ number of PV cells surrounded by WFA & ↓ intensity of WFA at 45 min; | Vazquez-Sanroman et al., 2016 |
| Ventral tegmental area (VTA) | VTA: ↓ number of PV cells surrounded by WFA at 45 min and 3 days; ↓ intensity of WFA at 45 min | |||||||
| Opioids | Species/sex | Age | Brain area | Treatment | Time after treatment | Behavior | PNN result | Citation |
| Heroin self-administration (100 µg/kg/infusion), IV | Rats/Male | Adult | Dorsal striatum | 3 hr/day X 16 days; Extinction 1 h/day X 15 days | 21 days abstinence; Extinction; Reinstatement | Self-administraition | Van den Oever et al., 2010 | |
| Nucleus accumbens (Nac) | NAc: Extinction: ↓ tenascin-R (180 & 160 kDa); Cue reinstatement: partially restored tenascin-R | |||||||
| Prefrontal cortex (PFC) | PFC: 21 days abstinence: ↓ synaptosomal tenascin-R (160 kDa), ↓ brevican - Bcan; (145 kDa); Extinction: ↓ Bcan (145 kDa); Cue reinstatement: ↑ Bcan (145 kDa) to pre-extinction levels | |||||||
| Heroin self-administration (0.075 mg/kg/infusion), IV | Rats/Male | Adult | Prefrontal cortex (PFC): Infralimbic (IL) and orbiotofrontal cortex (OFC) | 6 h/day X 10 days | 1 or 30 days abstinence | Self-administration | PFC- IL and OFC: 1 Day: ↑ number of WFA cells | Roura-Martinez et al., 2020 |
| PFC- OFC: 30 Days: ↑ number of WFA cells | ||||||||